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2. Osteoporosis Pasca Menopause

OSTEOPOROSIS

Oleh Dr H Subagyo SpB - SpOT

  OSTEOPOROSIS PASCA MENOPAUSE

Postmenopause

Sebelumnya perlu kita ketahui bahwa menopause adalah saat dimana terjadi berhentinya menstruasi secara permanen akibat berkurangnya atauhilangnya aktivitas ovarium. Menopause adalah tidak haid selama 12 bulan berturut-turut.Penelitian pendahuluan oleh Agung, Akbar, Loekmono, Tedjo (tidak dipublikasikan) bahwa di Surakarta didapatkan sebagian besar perempuan mengalami menopause pada usia < 50 tahun. 

Usia rata-rata seorang perempuan mengalami onset menopause pada suatu penelitian pada perempuan kulit hitam diAmerika Serikat oleh Bromberger dkk adalah 49,3 tahun. Sedangkan di Inggrisdan Amerika Serikat berumur 51 tahun ( Brown, 2002; Palmer, 2003). Fase klimakterik atau menopause dibagi dalam beberapa fase sebagai berikut :(Baziad, 2003; Luzuy, 2007)

 

Gejala Menopause

 

1.        Fase pra menopause adalah fase antara usia 40 tahun dan dimulainya fase klimakterik. Fase ini ditandai dengan siklus haid yang tidak teratur, dengan perdarahan haid yang memanjang dan jumlah darah haid yang relatif banyak dan kadang-kadang disertai nyeri haid.

 

Usia Menopause dan Faktor-faktor yang Mempengaruhi

 

2.        Fase peri menopause merupakan fase peralihan antara pramenopause dan post menopause. Fase ini ditandai dengan siklus haid yang tidak teratur.
3.        Fase post menopause bila telah mengalami menopause 12 bulan menuju ke senium. Senium adalah post menopause lanjut, yaitu setelah berusia 65 tahun. Batasan usia post menopause terjadi pada usia 50 – 65 tahun.

 

 

Usia Reproduktif Wanita

 

Postmenopause adalah masa setelah menopause sampai senium setelah 12bulan amenore. Hilangnya aktivitas ovarium mengakibatkan rendahnya kadarestradiol berada antara 20 – 30 pg/ml, sehingga endometrium menjadi atrofi dantidak haid. Pada wanita gemuk masih dapat ditemukan kadar estradiol darah yangtinggi, oleh karena jaringan lemak atau adipose, tetapi walaupun dapat mencegahtimbulnya osteoporosis namun masih belum dipahami alasan seperti itusepenuhnya. Perempuan yang sudah amenore kurang dari usia 40 tahun disebutsebagai menopause prekoks. Apabila seorang perempuan mengalami menopauselebih awal dari usia rata – rata seorang menopause antara 40-45 tahun dan tidak terdapat faktor-faktor yang menyebabkan menopause prekoks hal ini disebutsebagai menopause awal (Carr, 2001; Lane, 2001; Baziad(1), 2003; Luzuy, 2007).

 

Perubahan densitas mineral tulang sesuai umur dengan status menstruasi

Pada beberapa orang penyusutan tulang lebih cepat dari pada orang lain.Secara umum, wanita menopause dapat mengalami penyusutan tulang normal (<3% pertahun). Pada wanita dengan siklus menstruasi yang teratur, setelah usia inidensitas tulang tidak bertambah atau berkurang, atau apabila penyusutan terjadimaka tidak lebih dari 0,5 % pertahun. Walaupun penyusutan tulang bervariasi,namun pada umumnya akselerasi penyusutan tulang terjadi 5-10 tahun setelahmenopause (3,0-5,0%) dan menurun setelah waktu tersebut (0,5-1,0%).Jumlahtotal penyusutan tulang kira-kira 15% dari jumlah massa tulang pada tahun-tahunpertama postmenopause dan jumlah penyusutan sepanjang hidup adalah 30-40%(Lewellyn, 1991; Riis, 1996).

Massa Tulang Pada Berbagai Tingkat Kehidupan

Penyusutan tulang terjadi bila resorpsi tulang lebih besar daripada pembentukan tulang. Pada trabekula tulang (vertebra lumbalis, femur, distal radius), puncak massa tulang tercapai sampai usia 35 – 40 tahun. Penyusutan tulang terjadi mulai usia 40- 45 tahun, 40 – 50 tahun 0,5 – 1,0% pertahun, 50 – 60 tahun 3,0 – 5,0% pertahun, > 60 tahun 5,0 – 10% pertahun. Pada korteks tulang (tulang panjang dari lengan dan tungkai), puncak massa tulang tercapai sampai usia 35 – 40 tahun. Penyusutan tulang mulai usia 40 – 45 tahun, dengan kecepatan penyusutan rata-rata0,5 – 1,0 % pertahun.

Efek estrogen terhadap kehilangan densitas tulang

Estrogen menyebabkan meningkatnya aktivitas osteoblast. Oleh karena itu,pada pubertas, ketika seorang perempuan masuk ke masa reproduksi, lajupertumbuhannya menjadi cepat selama beberapa tahun. Akan tetapi, estrogen juga mempunyai efek poten lainnya terhadap pertumbuhan tulang rangka yaitumenyebabkan terjadinya penggabungan awal dari epifisis dengan batang daritulang panjang. Efek ini lebih kuat pada perempuan dibandingkan dengan efek serupa dari testoteron pada pria. Sebagai akibatnya, pertumbuhan perempuan lebihcepat daripada pria. Perempuan kasim (eunuch), yang sama sekali tidak memproduksi estrogen biasanya tumbuh beberapa inci lebih tinggi daripadaperempuan dewasa normal, karena epifisisnya tidak bergabung lebih cepat(Guyton, 1997; Lane, 2001).

Sesudah menopause, hampir tidak ada estrogen yang diekskresikan olehovarium. Kekurangan ini akan menyebabkan berkurangnya osteoblast pada tulang,berkurangnya matriks tulang dan berkurangnya deposit kalsium dan fosfat tulang.Pada beberapa wanita efek ini sangat hebat sehingga menyebabkan osteoporosis.Estrogen menghambat sekresi berbagai sitokin seperti IL-1, IL-6 dan TNF-a dansitokin ini akan membantu perkembangan osteoclast. Terdapat reseptor estrogen diosteoblast dan memberi efek langsung pada reseptor tersebut (Ganong, 2003;Guyton, 1997).

Daerah aksi potensial dari estrogen termasuk :

(i)                   efek pada produksisitogen sel T,

(ii)                 efek pada stromal atau sel-sel osteoblasttik untuk merubahproduksinya menjadiRANKLatauOsteoprotegerin(OPG),

(iii)                menginhibisilangsung dari osteoclast terdeferensiasi dan

(iv)                efek pada formasi tulang yangdimediasi oleh osteoblast atau osteosit untuk meningkatkan respon terhadap gayamekanik yang dimulai dari sel ini.

Resorpsi yang berlebihan dapat berakibathilangnya struktur trabekular (Baldock, 2004; Raisz, 2005; Adnan, 2008).

Pada wanita post menopause dengan menurunnya estrogen akan mempengaruhi daerah aksi potensial tulang seperti sel T, stromal dan sel monosit, osteoblast, sel endotelial dan osteoclast. Estrogen pada tulang mempunyai 2 signal reseptor yaituestrogen receptor alfa (ER-a) danestrogen receptorbeta (ER- b). ER-a berasal dari translasi 6,8-kilobase mRNA mempunyai kandungan 8exonyang merupakan derivat dari genrantai panjang kromosom 6. Mempunyai berat molekul yang diperkirakan sebesar66000 dengan 595 asam amino.Reseptor alfa mempunyaihalf lifediperkirakan 4-7 jam merupakan protein rapid turnover. Sedangkan reseptor beta baru di tandailokasi gen yang berasal dari kromosom 14, q22-q24. ER-b 96% asam aminohampir sama dengan ER- a ( Speroff, 2005). 

ER-apredominan secara isoformpada tulang korteks dan didistribusi secara luas dan cepat pada osteoblast danosteoclast sedangkan ER-b predominan pada trabekular diekspresikan sebagianbesar ke jaringan epitel dan mesenkimal termasuk osteoblast namun ekspresi keosteoclast masih dianggap kontroversial (Lindsay, 1996; Purdie, 2004; Raisz,2005; Weitzmann, 2006; Lerner, 2006).

Efek progesteron pada massa tulang

Progesteron dibagi dalam 2 bentuk, yaitu progesteron alamiah dan sintetik.Contoh dari progesteron alamiah hanya satu, yaitu progesteron.Progesteronsintetik dibagi dalam dua bentuk, yaitu struktur kimia menyerupai progesterone(turunan progesteron) dan struktur kimianya mirip dengan struktur kimiatestoteron (turunan testoteron).Progesteron sintetik turunan progesteron dibagilagi dalam 2 bentuk turunan yaitu turunan pregnan dan nonpregnan.Turunanpregnan mengandung komponen asetilat dan nonasetilat.Demikian juga halnyadengan progesteron sintetik turunan testetoteron dibagi dalam 2 bentuk yaitu jenisgugus etinil dan tidak gugus etinil.Kelompok gugus etinil dibagi dalam 2kelompok yaitu turunan estran dan gonan.Progesteron sintetik turunan progesteron sangat sedikit mempengaruhimetabolisme lipid HDL, dan pada umumnya tidak perlu pengaktifan terlebihdahulu di hati. Medroksiprogesteron asetat memiliki khasiat androgenik melaluipenambahan aktivitas enzim 5- -reduktase, sehingga terjadi penurunan kadartestoteron serum. Progesteron disimpan dalam lemak diberikan dalam dosis tinggi(150mg) akan tersimpan berupa depot (Baziad (2), 2003).

Progesterone

Reseptor progesteron diinduksi oleh estrogen pada tingkat transkripsional.2 bentuk yaitu sebagai penyelenggara transkriptional, mengalami sistem transkripsi yang kompleks.Masing-masing bentuk merupakan protein polipeptidayang termasuk kedalamstruktur aktivitas hormon yang terikat dan aktivitas reseptor. Berat molekuleramino,dengan reseptor estrogen terhadap protein; pada kasus ini penghambatan reseptorestrogen hanya pada keadaan yang kritis dan akan berlanjut pada aktivator(128-165 asam amino tergantung dari spesies) (Compston, 2001; Speroff, 2005).

Pada reseptor progesteron, TAF-1 berlokasi di 91 segmen yang beradapada ujung atas DNA binding domain.TAF-2 berlokasi di hormon bindingdomain.Aktivitas transkrip pada hormon-binding domain akan melepaskan suatufragmen sebanding dengan aktivitas lengan panjang hormon yang mengaktifkan. Melebihi dari TAF-1 sendiri(Compston, 2001; Speroff, 2005).

Komponen progesteron juga mempengaruhi densitas tulang, meskipuntidak sebaik estrogen.Mekanisme progesteron pada metabolisme tulang belumdiketahui pasti.Efek progestin terhadap metabolisme tulang relatif sedikitdiketahui.Pada orang normal sel osteoblasttik mengekspresikan reseptorprogesteron dan menstimulasi proliferasi dan diferensiasi sel dan menunjukanefek antagonistik terhadap reseptor estrogen (Speroff, 2005).

Ada beberapa progesterone yang digunakan secara klinis seperti19nortestoterone derivatediketahui memberikan efek baik pada tulang, walaupunsecaraevident basemasih kontroversial. Suatu persoalan bahwa menurunnyaovarium karena produksi progesteron akan merubah densitas mineral tulang masihmerupakan kontroversial.

Penelitian Prior, dkk melaporkan bahwa penurunandensitas tulangspinepada wanita dengan siklus anovulatory atau tanpa fase luteal keduanya akan mereduksi produksi progesteron ovarium.

Diagnosis Osteoporosis

Diagnosis dapat menggunakan pemeriksaan laboratorium untuk mendapatkan nilai dasar dan mencari penyebab sekunder yang berpotensi menyebabkan osteoporosis, bersama dengan pengukuran bone mineral density untuk menilai kehilangan tulang dan memperkirakan risiko fraktur.Biopsi tulang dapat menjadi indikasi pada situasi tertentu.

Pada kasus osteoporosis dapat dilakukan pemeriksaan berikut ini:

ü  Pemeriksaan darah rutin

ü   Kimia darah, termasuk kalsium, fosfat, creatinine, liver function test, elektrolit

ü  Thyroid-stimulating hormone (TSH)

ü  25-Hydroxyvitamin D level

Tingkat kalsium dapat mencerminkan adanya penyakit yang mendasari. Hiperkalsemia berat dapat mencerminkan keganasan atau hiperparatiroidisme. Selain itu, hipokalsemia memberikan kontribusi terhadap osteoporosis. Tingkat kalsium, fosfat, dan alkaline phosphatase biasanya normal pada orang-orang dengan osteoporosis primer, walaupun alkaline phosphatase dapat meningkat selama beberapa bulan setelah fraktur. Untuk membantu diagnosis osteomalacia, diambil tingkat alkaline phosphatase, kalsium, fosfat, dan 25(OH) vitamin D.

Disfungsi tiroid dihubungkan dengan osteoporosis, sehingga sebaiknya dipastikan kadar tiroid.

Kurangnya vitamin D memudahkan seseorang terkena osteoporosis.

Pemeriksaan laboratorium lainnya digunakan untuk mengevaluasi penyebab sekunder osteoporosis.

Pemeriksaan tersebut adalah:

 

ü  Kalsium urin dua puluh empat jam untuk menilai hiperkalsiuria

ü  Tingkat PTH

ü  Tingkat Thyrotropin  (bila sedang mendapat terapi pengganti tiroid)

ü  Tingkat testosterone dan gonadotropin

ü  Laju endap darah (LED) dan C-reactive protein (CRP)

ü  Kortisol bebas urin dan pemeriksaan untuk hipersekresi adrenal

ü  Serum protein electrophoresis (SPEP) dan urine protein electrophoresis (UPEP)

ü  Antigliadin dan antiendomysial antibodies untuk celiac disease

ü  Serum tryptase, urine N-methylhistamine untuk mastocytosis

ü  Biopsi sumsum tulang bila dicurigai kelainan hematologi

Kadar kalsium urin dua puluh empat jam dapat membantu menyingkirkan benign familial hypocalciuric hypercalcemia (FHH) dimana tingkat kalsium urin rendah. Peningkatan PTH selain menunjukkan hiperparatiroidisme, dapat ditemukan pada FHH. Para ahli berbeda pendapat mengenai pemeriksaan thyrotropin walaupun ada riwayat terapi hormon tiroid; namun sebuah studi menunjukkan berkurangnya bone mineral density pada collum femur pada wanita dengan hipotiroidisme dan hipertiroidisme subklinis. Pemeriksaan LED dan CRP kadang-kadang dilakukan, tergantung praktisi. SPEP dan UPEP digunakan untuk menyingkirkan multiple myeloma. SPEP dapat juga menyingkirkan plasma cell dyscrasia. Riwayat feses lembek dengan anemia dipikirkan adanya celiac sprue, yang berasosiasi dengan 5% kasus-kasus osteoporosis. Pasien-pasien dengan anemia, terutama yang berusia lebih dari 60 tahun, juga sebaiknya di evaluasi untuk multiple myeloma dengan elektroforesis protein serum dan urin. Cushing syndrome jarang terjadi, namun jika ada, dapat menyebabkan osteoporosis yang progresif secara cepat. Pemeriksaan yang diperlukan untuk Cushing syndrome adalah kadar kortisol bebas dalam urin atau overnight dexamethasone suppression testing. Zat besi dalam darah dan ferritin berguna jika dicurigai ada malabsorpsi atau hemochromatosis.

Sebuah studi dari Tannenbaum mengevaluasi 173 wanita sehat (berusia 46 – 87 tahun) untuk penyebab sekunder osteoporosis dan menemukan bahwa 55 (32%) memiliki kelainan tulang atau metabolisme mineral yang tidak terdiagnosis.

Penanda biokimia dari bone turnover mencerminkan formasi tulang dan resorpsi tulang. Kedua penanda ini (untuk formasi dan resorpsi) dapat meningkat pada keadaan-keadaan high-bone-turnover (misalnya pada osteoporosis pasca menopause) dan dapat berguna pada beberapa pasien untuk monitoring respon dini terhadap terapi.

 Penanda serum dari pembentukan tulang (penada ini merupakan produk-produk osteoblast) yang ada saat ini adalah:

ü  Bone-specific alkaline phosphatase (BSAP)

ü  Osteocalcin (OC)

ü  Carboxyterminal propeptide of type I collagen (PICP)

ü  Aminoterminal propeptide of type I collagen (PINP)

Penanda urin untuk resorpsi tulang (merupakan produk-produk osteoclast) termasuk berikut ini: -    Hydroxyproline

ü      Free and total pyridinolines (Pyd)

ü      Free and total deoxypyridinolines (Dpd)

ü      N-telopeptide of collagen cross-links (NTx)

ü      C-telopeptide of collagen cross-links (CTx)

Sedangkan penanda resorpsi tulang dari darah adalah:

ü      Cross-linked C-telopeptide of type I collagen (ICTP)

ü      Tartrate-resistant acid phosphatase

ü      NTx

ü      CTx

Dari tes-tes tersebut, yang paling sering digunakan dalam praktek klinik adalah BSAP, OC, NTx urin dan CTx serum.

BSAP dapat meningkat sedikit pada pasien-pasien dengan fraktur. Selain itu, pasien-pasien hiperparatiroidisme, Paget disease, atau osteomalacia dapat mengalami peningkatan BSAP. OC serum, bila tinggi, mengindikasikan osteoporosis dengan high-turnover. Elevasi NTx urin (>40 nmol kolagen tulang ekuivalen per mmol kreatinin urin) mengindikasikan keadaan high trunover. Tingkat NTx dapat juga digunakan untuk monitor respon terhadap pengobatan antiosteoporotik.

Terdapat kontroversi signifikan mengenai penggunaan penanda biokimia ini, dan terdapat kekhawatiran mengenai variabilitas intra-assay dan interassay. Dibutuhkan studi lanjut mengenai kegunaan klinis penanda ini dalam manajemen osteoporosis.

Radiografi dengan x-foto direkomendasikan untuk menilai integritas kerangka secara keseluruhan. Untuk mendiagnosis osteoporosis, x-foto dapat

menjadi indikasi jika pasien dicurigai fraktur atau jika pasien kehilangan tinggi badan lebih dari 1,5 inci.

Pada pasien simptomatik, ambil radiografi dari area yang bergejala. Lateral spine radiography dapat dilakukan pada pasien asimptomatik yang dicurigai fraktur vertebra, pada mereka yang tinggi badannya berkurang tanpa gejala lainnya, atau yang mengalami nyeri pada vertebra torakal atau lumbar atas. Seri skoliosis berguna untuk mendeteksi fraktur vertebra.

Penemuan radiografi dapat berarti adanya osteopenia, atau kehilangan tulang, walaupun tidak dapat digunakan untuk diagnosis osteoporosis. Menggunakan metacarpal kedua atau metafisis dari tulang panjang, jumlah lebar kortikal harusnya paling sedikit sama dengan lebar medular. Kemungkinan ada osteopenia jika jumlahnya kurang dari lebar medular. Radiografi juga dapat menunjukkan fraktur atau kondisi lainnya seperti osteoarthritis, disc disease, atau spondylolisthesis. Radiografi dengan x-ray tidak setepat dengan tes bone mineral density. Karena osteoporosis lebih banyak mempengaruhi tulang trabekular daripada kortikal, radiografi tidak menunjukkan perubahan osteoporosis sampai mengenai tulang kortikal.Tulang kortikal tidak terpengaruh osteoporosis sampai lebih dari 30% kehilangan tulang terjadi.Kira-kira 30 – 80 % mineral tulang harus hilang sampai penampakan lusent pada radiografi dapat terlihat. Sehingga, radiografi dengan x-ray merupakan modalitas yang tidak sensitif dalam mendiagnosis osteoporosis.

MRI dapat berguna dalam identifikasi fraktur-fraktur. Menggunakan  suppresi lemak, edema sumsum konsisten dengan fraktur dapat dilihat sebagai area hipointens pada T1-weighted. MRI merupakan modalitas yang sangat sensitif dan diyakini beberapa orang merupakan metode diagnostic imaging pilihan pertama dalam deteksi fraktur akut, seperti fraktur sakral.

MRI dapat digunakan untuk membedakan antara fraktur akut dan kronik dari vertebra dan stress fracture pada proximal femur.Fraktur osteoporotik memperlihatkan perubahan-perubahan karakteristik dalam sumsum tulang yang membedakan mereka dari bagian-bagian lain kerangka yang tidak terlibat dan vertebra sebelahnya.

MRI dapat berguna dalam penilaian metabolic bone disease.

Bone scanning menilai fungsi dan metabolisme jaringan dari organ-organ dengan menggunakan radionuclide (technetiu,-99m) yang memancarkan radiasi sesuai dengan yang menempel pada struktur target.Merupakan modalitas yang tidak spesifik, namun sangat sensitif untuk mendeteksi abnormalitas tulang karena peningkatan aktivitas osteoblasttik (seperti pada compression fractures) menyebabkan peningkatan konsentrasi radionuclide tracer.

Gambar dapat diperoleh dalam 3 fase dari proses bone scanning. Fase-fase ini adalah immediate-flow study, immediate static blood pool study, dan delayed static study. Fraktur akut terlihat dalam semua fase bone scanning dan tetap diluar nilai normal sampai selama 2 tahun.

Biopsi tulang dapat membantu eksklusi dari kondisi patologis seperti multiple myeloma, yang dapat menyebabkan fraktur patologis.Biasanya, biopsi dari iliac crest dilakukan baik sebagai prosedur minor maupun di dalam kamar operasi.

Tetracycline double labeling adalah sebuah proses yang digunakan untuk menghitung data bone turnover. Pada prosedur ini, pasien diberikan tetracycline, yang terikat pada tulang yang baru dibentuk. Ini terlihat pada sampel biopsi sebagai fluoresen linier. Dosis kedua tetracycline diberikan 11 – 14 hari setelah dosis pertama; ini terlihat pada sampel biopsi sebagai garis fluoresensi kedua. Jarak antara 2 label fluoresensi dapat diukur untuk kalkulasi jumlah tulang yang dibentuk pada interval tersebut.

Selain itu dapat dilakukan biopsi vertebral body saat melakukan prosedur terapi seperti kyphoplasty atau vertebroplasty untuk fiksasi dari vertebral compression fracture.

Walaupun biopsi tulang jarang digunakan untuk menyingkirkan neoplasma dan penyakit metabolik tulang lainnya, kadang-kadang dapat digunakan untuk menentukan kehilangan tulang secara kuantitatif, menggunakan quantitative histomorphometric technique. Pemeriksaan histologi dari tulang osteoporotik dapat menunjukkan penipisan trabekula dan perforasi ireguler dari trabekula, mencerminkan ketidakseimbangan resorpsi tulang yang di-mediasi osteoclast.

  • Pengukuran Massa Tulang

Alat yang sering dipakai untuk mengukur massa tulang adalah Densitometri. Densitometri ini tersedia beberapa macam. Densitometri dapat diklasifikasi berdasarkan kemampuannya mengukur daerah tulang tertentu:

a.        Densitometri sentral, yang memiliki kemampuan mengukur spine dan hip. Alat ini juga dapat mengukur forearm dan total body.
b.       Densitometri perifer, yang memiliki kemampuan mengukur pergelangan tangan, tumit, jari, dan lain-lain.

Berdasarkan jenis tekonologinya terdapat dua macam densitometri, yaitu x-ray based dan ultrasound based.

Lokasi kerangka dibagi menjadi dua klasifikasi:

a.       Central sites, yaitu vertebral column, ribs, dan sternum, pelvis, dan proximal femur.
b.       Peripheral sites, termasuk lengan dan tungkai (namun tidak termasuk proksimal femur).

Untuk densitometri sentral, terdapat dua alat, yang disebut Dual-energy x-ray absorptiometry (DXA / DEXA) dan quantitative computed tomography (QCT). Central DXA merupakan alat yang baik, karena:

a. Merupakan standard utama (gold standard).
b. Tehnik yang digunakan dengan alat ini sudah dikenal banyak profesional.
c. Presisi alat ini sangat baik.
d. Efek radiasinya rendah (effective dose: 1-3 uSv).
e. Banyak digunakan untuk studi epidemiologi.
f. Banyak dikenal karena adanya hubungan antara bone mineral density dengan resiko patah tulang.
g. Banyak digunakan untuk penelitian obat osteoporosis.

 

Alat DXA di Rumah Sakit Jakarta

Untuk peripheral densitometry, terdapat beberapa alat, yaitu:

a.        Peripheral DXA (pDXA)
b.       Single X-ray Absorptiometry(SXA)
c.        Peripheral QCT (Pqct)
d.       Quantitative Ultrasound (QUS)
e.        Radiographic Absorptiometry (RA)

Prinsip kerja absorptiometry adalah sebagai berikut.X-ray mengeluarkan energi berupa photon energy. Bila sinar ini terhalang elektron, akan terjadi pelemahan dari jumlah photon energy yang berasal dari sinar x-ray (attenuation). Besarnya attenuation ini ditentukan oleh tebal dan kerasnya jaringan tubuh yang dilalui oleh x-ray tersebut. Makin keras (dense) jaringan tubuh, makin banyak berisi electron. Makin banyak kandungan electron, maka akan semakin tinggi kemampuan jaringan untuk meng-atenuasi photon yang ada dalam x-ray. Jika tingkat perbedaan atenuasi ini dapat dihitung secara kwantitatif, maka kita dapat menghitung massa jaringan tersebut. Jika hanya menggunakan single energy x-ray beam, incident beam (Io) yang ter-atenuasi sesuai dengan jumlah massa yang dilaluinya dan sinar yang keluar (I) dapat di deteksi. Namun kita tidak dapat membedakan mana yang tulang atau jaringan lunak atau keduanya. Bone mineral density dari alat-alat yang dibuat oleh pembuat / pabrik yang berbeda tidak dapat dibandingkan, akibat:

a.       Berbeda metode penghasil dual energy
b.       Berbeda cara kalibrasi
c.        Berbeda detektor
d.       Software edge detection berbeda

  1. e.        Berbeda region of interest (ROI)

Dibandingkan DXA, QCT memiliki keuntungan dan kerugian. Keuntungan dari penggunaan QCT adalah:

a.        Tidak seperti DXA, QCT memungkinkan mengukur volumetric bone mineral density (misal, mg/cm3)
b.       Pengukuran semacam ini tidak tergantung dari luas area vertebra sehingga tidak menimbulkan kesalahan perhitungan
c.        QCT ini berguna bagi pasien yang memiliki berat badan yang ekstrim
d.       Memiliki kemampuan hanya menghitung cancellous bone
e.        Minimal atau tidak ada efek dari penyakit degeneratif tulang punggung

Sedangkan kerugian penggunaan QCT adalah:

a.       Presisi nya lebih jelek dari PA spine DXA namun diperbaiki dengan 3D (spiral CT)
b.       Dosis radiasi lebih besar daripada DXA

QUS merupakan alat yang berbeda daripada DXA. Alat ini tidak menyebabkan radiasi, karena QUS menggunakan gelombang suara (getaran mekanik), sedangkan alat-alat x-ray (DXA, pDXA, SXA, QCT, RA) menggunakan ionizing radiation. Namun QUS tidak dapat mengukur bone mineral density.Saat ini, QUS hanya dapat digunakan untuk tulang perifer.

Pada pengukuran BMD, ada beberapa parameter yang diukur.

1)       BMC = bone mineral content (g)

2)       Area = panjang x lebar (cm2)

3)       BMD = bone mineral density (g/cm2).

BMD = BMC / area

4)       T- score.

T-score merupakan perbandingan dari BMD pasien saat pemeriksaan dengan BMD saat puncak massa tulang. T-score menggunakan reference database sebagai perbandingan. Biasanya digunakan database uniform Caucasian (non-race adjusted) male / female normative database, untuk semua etnik. T-score dihitung dengan rumus sebagai berikut:

 T-score = (BMD pasien – BMD referensi) / SD dari referensi 

5)       Z-score.

Z-score merupakan perbandingan dari BMD pasien dengan BMD dari grup usia yang sama. Untuk perhitungan Z-score, reference database yang digunakan sebaiknya khusus untuk etnik nya atau etnik yang hampir sama yang ada dalam data mesin. Jadi untuk perhitungan Z-score, etnik pasien sebagai reference database harus digunakan. Z-score dihitung dengan rumus:

Z-score =  (BMD pasien – BMD referensi) / SD referensi

Untuk melaporkan BMD, terdapat beberapa hal yang perlu diperhatikan:

1)       Pada wanita pasca menopause dan pria > 50 tahun,

a.        T-score lebih dipilih
b.       WHO densitometric classification dapat digunakan

2)       Pada wanita menopause dan pria < 50 tahun

a.        Z-score lebih dipilih daripada T-score; terutama penting pada anak-anak
b.       Z-score sebesar -2,0 atau lebih rendah didefinisikan “dibawah normal bila dibandingkan dengan usianya”, dan z-score diatas -2,0 didefinisikan “dalam batas normal bila dibandingkan dengan usianya”.
c.        Osteoporosis tidak dapat di diagnosa pada pria dibawah 50 tahun hanya berdasarkan nilai BMD saja
d.       WHO diagnostic criteria mungkin bisa digunakan pada wanita perimenopause

World Health Organization Diagnostic Criteria

Classification

T-score

Normal

Lebih dari / sama dengan -1,0

Osteopenia

Diantara -1,0 dan -2,5

Osteoporosis

Kurang dari / sama dengan -2,5

Severe osteoporosis

Kurang dari / sama dengan -2,5

Riwayat fraktur fragilitas

 

Selain untuk diagnosis osteoporosis, pengukuran BMD juga berguna untuk menilai resiko fraktur yang akan datang. Pengukuran BMD di semua tempat akan memprediksi risiko fraktur secara global. BMD dapat digunakan pada algoritma tertentu, seperti pada penggunaan FRAX. FRAX dibuat oleh WHO, dan merupakan Fracture Risk Assessment Tool.Alat ini digunakan untuk menduga resiko fraktur 10 tahun mendatang. FRAX menggunakan faktor-faktor klinis, yaitu:

 

a)       Demografi (berat badan, tinggi badan, usia dan jenis kelamin)

b)       Riwayat fraktur pada pasien

c)       Riwayat orang tua dengan fraktur panggul

d)       Konsumsi alkohol dan merokok saat ini

e)       Penggunaan glukokortikoid

f)        Rheumatoid Arthritis

g)       Secondary osteoporosis

h)       BMD leher femur (bila ada)

Dalam menjawab pertanyaan pada FRAX, terdapat beberapa definisi yang perlu diketahui. Definisi-definisi tersebut adalah:

1)       Apa artinya belum pernah di terapi?

(i)         Tidak ada terapi osteoporosis non-bisphosphonate dalam setahun terakhir

(ii)        Tidak menggunakan terapi Bisphosphonate dalam 2 tahun terakhir

2)       Apa artinya ”pernah fraktur”?

(i)         Fraktur pada usia dewasa yang terjadi secara spontan atau trauma ringan

3)       Apa artinya riwayat fraktur panggul pada orang tua?

Salah satu orang tuanya pernah fraktur panggul akibat trauma ringan

4)       Glukokortikoid

Pernah minum glukokortikoid lebih dari 3 bulan, prednisolone dengan dosis lebih dari atau sama dengan 5 mg per hari.

5)       Alkohol 3 unit atau lebih per hari

1 unit = 1,5 oz liquor; 10 oz beer; 3 - 4 oz wine

BMD juga dapat digunakan untuk monitoring terapi.Pengukuran serial dapat menentukan kapan mulai dilakukan terapi atau mengetahui respon dari suatu pengobatan. Bila perubahan BMD yang diharapkan terjadi sama atau melebihi dari LSC, tes kedua dilakukan. LSC adalah least significant change, yaitu jumlah perubahan pada densitas tulang yang dibutuhkan, agar dapat dipastikan secara statistik bahwa benar-benar ada perubahan yang terjadi.

Interval pemeriksaan BMD sebaiknya ditentukan kasus per kasus. Pemeriksaan dilakukan umumnya satu tahun setelah terapi, namun dapat lebih lama dari setahun jika efek yang diinginkan baru terjadi. Bila terdapat keadaan dimana kehilangan tulang terjadi dengan cepat, maka tes sebaiknya dilakukan lebih cepat.

Monitoring terapi central skeleton menggunakan Bone Density Test, umumnya melihat tulang punggung. Perubahan BMD paling cepat terjadi di tulang punggung, walaupun ada penyakit degeneratif. Proximal femur juga dapat digunakan untuk monitoring; Namun, perubahannya butuh waktu lebih lama.Peripheral tidak direkomendasi untuk monitoring.Bila terdapat BMD yang stabil atau meningkat, maka hasilnya dikatakan positif.

Jika ternyata terjadi penurunan BMD (pada 95% confidence), periksa apakah pasien minum obat teratur. Selain itu cari kemungkinan adanya penyakit atau kondisi lainnya yang dapat menjadi penyebab. Idealnya, jika pasien mendapatkan terapi, dilakukan tes satu tahun kemudian selama dua tahun. Kemudian tes dilakukan setiap dua tahun jika stabil atau BMD meningkat. Jika pasien memakai glukokortikoid, sebaiknya dilakukan cek dalam 6 bulan lalu 6 – 12 bulan sampai stabil.

Bila hasil BMD berbeda dari yang kita harapkan saat monitoring, bandingkan gambar hasil scan secara konsisten, baik secara posisi dan analisis. Lihat kemungkinan adanya artefak baru atau tidak diinginkan. Mungkin juga ada kesalahan peralatan atau software. Untuk tujuan ini, rekaman hasil pemeriksaan harus terdokumentasi dengan baik.

Untuk memperoleh hasil DXA yang baik, posisi pasien memegang peranan penting. Masing-masing bagian memiliki ketetapan agar hasil pengukuran lebih akurat.

Untuk PA spine, ketentuannya adalah:

(i)                   Posisi tulang punggung tepat di tengah meja scanner

(ii)                 Luruskan pasien sesuai tengah scanner, sehingga tulang punggung lurus (not tilted)

(iii)                Naikkan tungkai dengan positioning block

(iv)                Kedua crista iliaca terlihat

(v)                 Scan termasuk middle L5 dan middle T12

(vi)                Perhatikan dengan benar

1.        Garis tepi Lateral vertebral
2.        Garis pemisah antara vertebra (intervertebral markers)

(vii)              Hilangkan artefak

(viii)             Untuk pasien dengan anomali segmentasi, hitung mulai dari crista iliaca ke atas (bottom up)

(ix)                Sekitar 84% populasi memiliki 5 lumbar vertebrae dengan iga terendah pada T12. 8% memiliki 4 lumbar vertebrae dengan iga terendah pada T11 atau T12. 7% memiliki 5 lumbar vertebrae dengan iga terendah pada T11. Sekitar 2% memiliki 6 lumbar vertebrae dengan iga terendah pada T12 atau L1.

Untuk panggul, perhatikan:

(i)                   Tempatkan kaki pada positioning device

(ii)                 Endo rotasi dengan sudut tertentu

(iii)                Tempatkan shaft of femur parallel terhadap scanner axis

(iv)                Trochanter minor terletak di bagian posterior

(v)                 Ukuran dari trochanter minor sebagai indikasi besarnya rotasi proximal femur

(vi)                Nilai BMD dipengaruhi oleh besarnya rotasi proximal femur dan posisi dari femoral neck ROI

(vii)              Internal atau external rotation menyebabkan peningkatan BMD

(viii)             Penyakit seperti osteoarthritis, fraktur, adanya fusi dapat mengganggu pengukuran

(ix)                Neck ROI harus tidak termasuk trochanter mayor

(x)                 Hindari ischium jika mungkin

(xi)                Keluarkan artifak (jika kecil dan tidak menutup tulang)

Untuk collum femur, ikuti rekomendasi pembuat alat. Biasanya terdapat ketentuan spesifik.

Untuk forearm scan:

(i)                   Forearm berada di tengah

(ii)                 Radius dan ulna lurus (sejajar dengan axis panjang dari meja)

(iii)                Distal cortex dari radius dan ulna kelihatan

(iv)                Tidak ada artefak

(v)                 Tidak ada masalah pada forearm (hardware, fusi, osteoarthritis, fraktur)

(vi)                Gunakan 33% (1/3) site of the radius untuk diagnosis

 

Total (whole) body positioning biasanya digunakan untuk body composition dan pediatrik. Ketentuannya adalah

(i)                   Luruskan pasien dengan scanner axis

(ii)                 Seluruh tubuh ada dalam batas scan

(iii)                Lengan di samping tubuh

(iv)                Lengan tidak boleh menempel tubuh

(v)                 Posisi tangan dan kaki tergantung pada pembuat alat

(vi)                Cek adanya artefak termasuk implan

(vii)              Penempatan ROI bervariasi tergantung rekomendasi pembuat alat.

Untuk lateral spine scan analysis perhatikan:

(i)                   Tidak digunakan untuk diagnosis osteoporosis

(ii)                 Ukur cancellous bone (corpus vertebra)

(iii)                Kegunaan untuk monitoring terbatas

(iv)                Posisi dekubitus memiliki presisi jelek

(v)                 Tulang iga yang melintang mempengaruhi analisa dari L1 atau L2

(vi)                Iliac crest overlap mungkin mempengaruhi analisis dari L4

(vii)              Hilangkan artefak. Posterior element tidak termasuk (sebagian besar perubahan degeneratif). Keluarkan / hindari aortic calcification

Follow up membutuhkan pengukuran yang konsisten. Bila pengukuran tidak konsisten, maka hasil follow up tidak dapat diandalkan. Untuk follow up scan, perhatikan:

(i)                   Posisi pasien konsisten

(ii)                 Analisis hasil pencitraan konsisten

(iii)                Area pencitraan harus semirip mungkin

Banyak artefak yang dapat ditemukan pada saat kita melakukan DXA scan. Berikut akan disebutkan apa saja arterfak yang dapat ditemukan.

1.       Artefak yang sering ditemukan

(i)                   Penyakit degeneratif

(ii)                 Fraktur

(iii)                Metal

2.       Penyakit degeneratif

(i)                   Penyakit degeneratif pada tulang punggung sering meningkatkan BMD

(ii)                 Osteoarthritis berat pada panggul mungkin meningkatkan bone mineral density pada collum femur atau total hip

(iii)                BMD pada trochanteric region tidak terpengaruh adanya severe osteoarthritis

3.       Fraktur tulang punggung

(i)                   Secara umum, fraktur meningkatkan bone mineral density

(ii)                 Fraktur kompresi vertebra mungkin kelihatan pada gambar DXA karena tinggi vertebra lebih rendah dibandingkan dengan vertebra didekatnya

(iii)                Pada kasus semacam ini, nilai bone mineral density meningkat densitasnya dibandingkan dengan vertebra di dekatnya

(iv)                Pada beberapa kasus, PA spine DXA image tidak memperlihatkan adanya fraktur (yang sebenarnya ada)

(v)                 Pada kasus semacam ini, bone mineral density yang lebih tinggi dari sekitarnya merupakan petunjuk terhadap kemungkinan adanya compression fracture

(vi)                Perbandingan terhadap lateral DXA image atau lumbar spine x-ray diperlukan untuk memastikan diagnosa

(vii)              Fraktur-fraktur harus dikeluarkan dari RIO untuk mencegah perhitungan bone mineral density yang salah

4.       Fraktur-fraktur lainnya

(i)                   Secara umum, fraktur meningkatkan bone mineral density

(ii)                 Hindari scanning terhadap panggul atau lengan dengan fraktur lama

5.       Contoh-contoh arterfak internal lainnya

(i)                   Penyakit-penyakit degeneratif

(ii)                 Surgical clips and hardware

(iii)                Fusi tulang punggung

(iv)                Aortic calcification

(v)                 Gastrointestinal contrast

(vi)                Stent

(vii)              Pacemaker

(viii)             IVC umbrella

(ix)                Calcium tablets

(x)                 Batu empedu

(xi)                Batu ginjal

(xii)              Kalsifikasi pankreas

(xiii)             Laminectomy defects

(xiv)             Paget’s disease

(xv)              Metallic devices

(xvi)             Vertebroplasty or kyphoplasty

(xvii)           Metastatic lesion

(xviii)          Osteoarthritis

(xix)             Osteoma

(xx)              Obesity

(xxi)             Fat panniculus

(xxii)           Heterotopic ossification

6.       Contoh-contoh artifak eksternal

(i)                   Kancing

(ii)                 Cincin umbilikus

(iii)                Retsleting

(iv)                Garter clip

(v)                 Bra clip

(vi)                Dompet

(vii)              Perhiasan atau Wrist band.

Pada pengukuran BMD dan BMC, dapat terlihat perubahan secara incremental.Mengingat hal ini, dapat kita gunakan untuk menilai hasil scan. L1 umumnya memiliki BMD yang ter rendah.BMC dan area meningkat tajam mulai L1 hingga L4.BMD cenderung meningkat mulai dari L1 hingga L3. Karena luas area L4 lebih besar dari L3 dan tidak sebanding dengan kenaikan BMC maka BMD L4 mungkin sama atau lebih rendah dari L3.

Pada penggunaan untuk diagnosis, central DXA menggunakan T-score yang terrendah dari dua site, PA spine, total hip dan femoral neck. Pada tulang punggung, biasanya dipilih menggunakan rata-rata dari L1-L4. Kecuali ada vertebra yang bermasalah (seperti fraktur, penyakit degeneratif fokal, pembedahan, dan lain-lain) sehingga harus dikeluarkan dari analisa. Pada panggul, gunakan T-score ter rendah dari total hip (total femur) atau femoral neck. Ward’s dan regio trochanter tidak digunakan untuk diagnosis osteoporosis atau untuk monitor terapi.

Ward’s region adalah daerah segitiga pada femoral neck yang terbentuk dari pertemuan 3 cancellous bundles (tensile, compressive, dan intertrochanteric). Pada DXA scans, Ward’s area berbentuk segi empat, yang letaknya bervariasi tergantung dari pembuat alat, dan tidak berhubungan dengan lokasi sebenarnya. Karena areanya kecil dan presisi nya buruk maka jangan gunakan Ward’s region untuk diagnosis atau follow up secara serial (atau untuk hal apapun kecuali penelitian).

Daerah L1-L4 merupakan daerah yang paling banyak dipilih untuk menegakkan diagnosis.Namun terdapat kriteria untuk mengeluarkan vertebra dari analisis. Vertebra yang mengalami kelainan anatomi akan dikeluarkan dari analisa jika:

(i)                   Mereka jelas-jelas abnormal atau tidak dapat diukur; atau

(ii)                 Ada perbedaan T-score lebih dari 1,0 SD dibandingkan dengan vertebra terdekat

Jika ada vertebra yang dikeluarkan, bone mineral density dari vertebra yang tersisa tetap dapat digunakan untuk menghitung T-score nya.Penghapusan vertebral body dari perhitungan dapat dilakukan oleh mesin-mesin baru secara otomatis. Namun kita dapat melakukan penghitungan manual untuk penghapusan dari vertebral body. Caranya adalah sebagai berikut:

(i)                   Formula: BMD = BMC / Area

a.        BMC adalah bone mineral content

(ii)                 Untuk kalkulasi manual: jika kita menghapus salah satu vertebra secara manual, jangan melakukan penghitungan bone mineral density dengan cara membagi rata

(iii)                Prosedur yang benar untuk kalkulasi manual adalah:

a.        Tambahkan nilai BMC bersama-sama
b.       Tambahkan semua nilai area
c.        BMC dibagi luas area
d.       Contoh: BMD dari (L1, L2, L4) adalah:

(BMC1 + BMC2 + BMC4) / (Area 1 + Area 2 + Area 4)

e.        T-score tidak dapat dihitung secara manual

Manajemen Osteoporosis Pasca Menopause

Osteoporosis pasca menopause adalah penyakit yang sering terjadi dengan spektrum luas, mulai dari terjadinya kehilangan tulang yang asimptomatis sampai ke fraktur panggul yang mengakibatkan disabilitas.

Konsensus dari National Institutes of Health mendefinisikan osteoporosis sebagai sebuah penyakit dimana terjadi peningkatan fragilitas kerangka yang disertai dengan densitas mineral tulang (bone mineral density, BMD) yang rendah (T score di bawah -2.5) dan deteriorasi mikroarsitektural. Diprediksi bahwa prevalensi fraktur akan meningkat di tahun 2025, namun saat ini ditemukan bahwa kurang dari seperempat dari semua wanita yang mengalami fraktur osteoporotik menerima pengobatan yang tepat untuk osteoporosis.

Fraktur terjadi karena deteriorasi kualitatif dan kuantitatif pada kerangka trabekular dan kortikal. Kualitas tulang tidak dapat diukur secara klinis, namun bone mineral denstiy dapat diukur secara cepat, aman, tanpa rasa sakit, akurat, tepat, dan relatif tidak mahal; beberapa metode dapat digunakan, dan diantaranya dual-energy x-ray absorptiometry adalah yang paling diandalkan saat ini. Massa tulang yang rendah pada lokasi kerangka manapun diasosiasikan dengan dengan peningkatan risiko fraktur secara bermakna. Faktor risiko lain termasuk usia lanjut, berat badan rendah, riwayat osteoporosis maternal, arah jatuh (jatuh ke arah belakang dan pada satu sisi merupakan kondisi yang paling mungkin menyebabkan fraktur), dan yang paling penting, adanya fraktur sebelumnya.

Rencana manajemen yang komprehensif untuk osteoporosis termasuk evaluasi pasien dengan risiko tinggi, eksklusi penyebab sekunder dari rendahnya bone mineral density, dan pemilihan terapi yang tepat. Riwayat dari fragility fracture (fraktur yang terjadi tanpa trauma yang cukup bermakna) pada wanita pasca menopause sangat mendukung diagnosis osteoporosis, walaupun tanpa pemeriksaan bone mineral density. Penyebab sekunder seperti hiperparatiroid primer, defisiensi vitamin D akibat kurangnya asupan, kurang paparan sinar matahari, atau malabsorpsi, dan multiple myeloma harus di eksklusi, terutama bila z score (angka standard deviation dari mean untuk suatu grup populasi dengan usia dan jenis kelamin yang spesifik) dari bone mineral density mengalami depresi (misalnya dibawah -2.00). Penanda biokimia dari bone turnover seperti N-telopeptide atau osteocalcin jarang membantu dalam menegakkan diagnosis atau pemilihan terapi, namun dapat digunakan untuk menentukan apakah terdapat percepatan tingkat hilangnya tulang, terutama saat beberapa tahun pertama dari masa menopause.

Beberapa hal perlu dipikirkan saat memilih penanganan yang akan digunakan. Terapi osteoporosis dapat menurunkan risiko fraktur sampai 50 persen, namun beberapa wanita tetap mengalami fraktur walaupun telah di terapi. Selain itu, perubahan gaya hidup dan penggunaan intervensi farmakologi merupakan komitmen seumur hidup. Oleh karena itu dalam menentukan terapi harus dipikirkan mengenai biaya, kepatuhan terhadap regimen pengobatan, dan keamanan. Selain itu terdapat persentase signifikan fraktur osteoporosis yang terjadi pada wanita dengan T score di atas -2.5 (T score merupakan angka standard deviation dari pengukuran bone mineral density yang diatas atau dibawah densitas tulang rata-rata normal). Pada beberapa kasus terdapat perbedaan cukup jauh antara T score tulang punggung dan panggul. Oleh karena itu, keputusan terapi sebaiknya tidak hanya dilakukan berdasarkan bone mineral density.

Tatalaksana Dari Osetoporosis

Penanganan medis termasuk pemberian kalsium yang cukup, vitamin D, dan obat anti-osteoporosis seperti bisphosphonate dan parathyroid hormone. Sebagai tambahan, penyebab yang mendasari dari osteoporosis (terutama yang dapat diobati) seperti hiperparatiroidisme dan hipertiroid harus disingkirkan atau diobati bila ditemukan.

Terapi pembedahan pada tulang punggung termasuk vertebroplasty dan kyphoplasty. Vertebroplasty dan kyphoplasty digunakan untuk manajemen osteoporotic vertebral compression fracture yang menimbulkan gejala nyeri hebat.

Asupan kalsium dan vitamin D yang cukup penting bagi siapapun pada usia berapapun, terutama pada masa anak-anak karena tulang sedang dalam proses maturasi. Pasien yang tidak memperoleh jumlah vitamin D dan kalsium yang cukup sebaiknya mendapatkan suplementasi oral. Diet yang termasuk Vitamin D dan kalsium yang cukup penting.

Pada 1994, National Institutes of Health memberikan rekomendasi asupan kalsium harian:

v  Birth to age 6 months - 400 mg/d

v  Age 6 months to 1 year - 600 mg/d

v  Age 1 to 10 years - 800-1200 mg/d

v  Age 11 to 24 years - 1200-1500 mg/d

v  Age 25 to 50 years - 1000 mg/d

v  Age 51 to 64 years - 1000 mg/d

v  Age 51 years and older (only women not on hormone replacement therapy [HRT]) - 1500 mg/d

v  Age 65 years and older - 1500 mg/d

v  Pregnant or lactating women - 1200-1500 mg/d

Rekomendasi asupan kalsium harian saat ini dari National Osteoporisis Foundation:

v  Age 1 to 3 years - 500 mg/d

v  Age 4 to 8 years - 800 mg/d

v  Age 9 to 18 years - 1300 mg /d

v  Age 19 to 49 years - 1000 mg/d

v  Age 50 years and older - 1200 mg/d

v  Pregnant and breastfeeding women age 18 years and younger - 1300 mg/d

v  Pregnant and breastfeeding women age 19 years and older - 1000 mg/d

Sayangnya vitamin D kurang mudah didapat melalui makanan yang umum dikonsumsi tetapi berpotensi, meskipun tidak selalu mudah, dimodifikasi "gaya hidup pilihan" yang mungkin memiliki efek dramatis pada tingkat vitamin D dalam tubuh adalah jumlah sinar matahari yang kulit terkena. Selama bertahun-tahun medis ortodoksi cenderung untuk mengandalkan pada fakta bahwa vitamin D dapat disintesis dalam tubuh pada paparan sinar matahari sebagai bukti pentingnya relatif rendah asupan makanan.Tapi saat ini kebanyakan orang tidak hanya bekerja di dalam ruangan, tetapi sangat disarankan untuk menutupi diri mereka secara bebas dengan tabir surya pada kesempatan langka ketika mereka mengekspos diri ke sinar matahari alami. Dan kekhawatiran ini bahkan lebih bermakna untuk orang tua, seiring kemampuan tubuh untuk mensintesis vitamin D dari sinar matahari berkurang dengan bertambahnya usia. Sayangnya sulit untuk mendapatkan asupan yang baik dari vitamin D dari Diet Barat konvensional, ikan, hati, telur dan sereal tertentu paling dapat diandalkan. Dan bertentangan dengan kepercayaan populer, produk susu itu sendiri bukan sumber yang sangat kaya kecuali secara khusus diperkaya dengan vitamin.

Kadang-kadang masyarakat bingung tentang waktu yang tepat untuk berjemur di bawah sinar matahari.Kebanyakan dari mereka mengidentifikasi bahwa berjemur di tengah hari dapat meningkatkan resiko terkena kanker kulit. Namun sebuah rekomendasi kesehatan yang baru justru menyarankan agar masyarakat mendapatkan paparan sinar matahari yang sedikit, tanpa menggunakan suncream, di saat pagi hari. Tujuh organisasi kesehatan telah mengeluarkan saran secara bersamaan tentang vitamin D alami yang didapat oleh tubuh dari paparan sinar matahari. Vitamin D ini dapat membuat tulang menjadi semakin kuat dan dapat melindungi Anda dari penyakit Osteoporosis. Cancer Research UK dan The National Osteoporosis Society juga menyetujui tentang paparan sinar matahari yang “sedikit dan sering”, selama beberapa kali seminggu dapat bermanfaat bagi kesehatan.

Pemerintah Inggris juga telah merekomendasikan secara resmi tentang pentingnya suplemen vitamin D bagi ibu hamil dan anak-anak di usia balita, namun para ibu masih banyak yang tidak sadar akan rekomendasi ini. Untuk lebih pastinya, para pakar kesehatan menyarankan agar para ibu berkonsultasi dengan dokter umum mereka mengenai hal ini. Di beberapa negara, musim panas memang terbatas lamanya. Namun, tidak perlu khawatir, saat musim dingin tiba, kadar vitamin D dalam tubuh masih dapat dijaga dengan mengonsumsi minyak ikan, hati, susu dan juga keju

Sinar matahari merupakan pencegah osteoporosis (keropos tulang) yang paling murah dan mudah didapat. Dengan mendapat paparan sinar matahari pagi minimal 10 menit setiap hari ditambah mengonsumsi makanan tinggi kalsium dan berolahraga secara rutin, osteoporosis dapat dicegah sedini mungkin.

Sinar matahari mengandung sinar ultraviolet yang dibutuhkan tubuh untuk mengaktifkan vitamin D yang akan menyalurkan kalsium dari usus ke tulang. Waktu yang tepat untuk mendapatkan paparan sinar matahari pukul 06.30-09.30. Sebaiknya tubuh yang terkena sinar matahari tidak dilindungi tabir surya maupun pakaian lengan panjang, agar pembentukan vitamin D tidak terhalang.

Upaya pencegahan dini ini paling efektif dilakukan pada usia 20-25 tahun ketika pertumbuhan tulang sedang mencapai masa puncak. Namun, upaya pencegahan ini harus tetap dilakukan setelah masa puncak pertumbuhan tulang terlewati.

Menurut Ketua Perkumpulan Warga Tulang Sehat Indonesia (Perwatusi) Cabang Semarang Bambang Priyanto, pencegahan dini osteoporosis dapat efektif diterapkan jika remaja sudah melakukan gaya hidup sehat. (DEN)

Penelitian DEPKES pemeriksaan densitometer sonografi pada 16 wilayah di Indonesia asupan kalsium 254 gr/hari ( sangat rendah) pada seseorang dengan osteopenia terjadi sebesar 41,7 %  pada wanita usia > 55 tahun, dengan kejadian osteopenia wanita 6x  lebih tinggi dibandingkan pria dan osteoporosis 2 x dibandingkan pria.

Kolesterol tinggi juga sudah lama diketahui peneliti berhubungan dengan osteoporosis. Pasien-pasien osteoporosis diketahui sering memiliki tingkat kolesterol yang lebih tinggi (yang juga memiliki penyumbatan arteri koroner yang lebih berat dan meningkatkan risiko stroke). Ada yang berpendapat bahwa ini disebabkan oleh oksidasi, yang menyebabkan kerusakan sel dan jaringan akibat dari paparan terhadap asam lemak dalam kolesterol terhadap molekul-molekul radikal bebas. Namun mekanisme jelas yang menghubungkan kedua hal ini masih belum sepenuhnya dimengerti.

Sebuah studi dari UCLA (University of California, Los Angeles extension) menemukan hubungan antara kolesterol tinggi dan osteoporosis dan mengidentifikasi cara sel-sel imun tubuh berperan dalam osteoporosis.  Penelitian ini dapat mengarah pada pendekatan-pendekatan baru dari sisi imunologi untuk mengobati osteoporosis. Pada studi, peneliti-peneliti UCLA berfokus pada low-density lipoprotein (LDL), yang sudah lama dikenal sebagai kolesterol ”jahat”. Mereka memeriksa bagaimana LDL yang teroksidasi, dalam kadar tinggi, mempengaruhi tulang. Mereka juga memeriksa apakah T cell memainkan peran dalam proses ini. Para peneliti mengisolasi T cell dari sampel darah manusia sehat, yang kemudian di kultur. Setengah dari T cell ini di kombinasi dengan LDL normal, sisanya dengan LDL teroksidasi.Para peneliti menstimulasi setengah dari T cells untuk mensimulasi respon imun dan setengah lainnya dibiarkan. Hasilnya, baik T sel yang tidak aktif maupun T cells yang teraktivasi menghasilkan RANKL, yang berperan dalam respon imun dan fisiologi tulang. RANKL ini menstimulasi sel-sel yang menghancurkan tulang.

Para peneliti kemudian melanjutkan eksperimen pada tikus, untuk meneliti lebih jauh bagaimana sistem imun berperan dalam kehilangan tulang. Setengah dari tikus-tikus ini diberi diet tinggi lemak mulai dari usia satu bulan, sedangkan grup kontrol mendapat diet normal. Pada usia 11 bulan, tikus dengan diet tinggi lemak menunjukkan tingkat kolesterol yang meningkat dan tulang-tulang yang lebih tipis.  Ketika T cells pada tikus dengan diet tinggi lemak diperiksa, mereka menemukan bahwa sel-sel bekerja secara berbeda dibandingkan dengan tikus dengan diet normal. T cells mengaktifkan gen yang memproduksi RANKL. RANKL juga muncul pada aliran darah hewan, memberikan sugesti bahwa aktivitas seluler ini juga berperan menyebabkan kehilangan tulang pada tikus.

 

T cells secara normal memang memproduksi sejumlah kecil RANKL sebagai respon imun. Namun ketika RANKL dihasilkan untuk periode yang panjang atau tidak pada waktunya, hal ini menyebabkan kerusakan tulang yang

berlebih. Pada tikus dengan diet tinggi lemak, kolesterol tinggi meningkatkan tingkat LDL teroksidasi, yang menyebabkan T cells terus menghasilkan RANKL.Penelitian ini dapat dilanjutkan dengan eksplorasi metode untuk mengendalikan respon T cell terhadap LDL teroksidasi, sehingga kehilangan tulang dapat dicegah atau diperlambat.

Pemberian hormon estrogen alamiah (HRT) telah dimulai sejak tahun 1960 dan didapatkan hasil sangat baik menekan gejala menopause (90-97%), meningkatkan masa tulang (5,5-7,5%) dan menekan risiko patah tulang osteoporosis tetapi setelah pemakian lebih dari 40 tahun yaitu ditahun 2002 terdapat kontroversi adanya masalah-masalah yang merugikan, sehingga banyak dokter menghentikan pemakaian HRT setelah 5-7 tahun.

Saat ini fitoestrogen yang terbuat dari tumbuhan dengan rumus kimia hampir sama dengan estradiol telah diteliti walaupun kemampuannya mengikat reseptor estrogen jauh dibawah hormon estrogen alamiah.

Salah satunya adalah Ganetein, satu fito estrogen,  dilaporkan menyembuhkan keluhan menopause hingga 78.2% dalam satu tahun pemberian dan meningkatkan bone mineral density sebesar 2,1-3,1%. Pada pemberian tiga tahun fitoestrogen, kalsium dan disertai senam osteoporosis terlihat peningkatan masa tulang sebesar 60-70 % dan jauh lebih baik dari pada hanya pemberian vitamin D, kalsium dan senam osteoporosis saja.

Hormon-hormon yang lemah, yang ditemukan dalam makanan alami tanaman, disebut Fitoestrogen.Makanan ini memiliki gizi yang berbeda yang membantu untuk membawa bantuan untuk beberapa masalah yang berkaitan dengan fase menopause. Sumber makanan dari beberapa fitoestrogen telah diteliti dan menunjukan potensi keuntungan yang tersedia dalam tanaman untuk mengobati dan merawat suatu kondisi dan usia yang terkait dengan hormon.

Banyak penelitian dan studi menunjukkan sumber makanan fitoestrogen memberikan manfaat kesehatan yang meliputi potensi berkurangnya kanker prostat, kanker payudara dan pengurangan risiko penyakit kardiovaskuler lain, perlindungan terhadap osteoporosis dan juga lebih dari satu gejala menopause.

Flavon, lignan, coumestans dan Isoflovones adalah kelompok utama fitoestrogen.Beberapa dari mereka adalah flavonoid. Sementara Isoflovones biasanya ditemukan dalam konsentrasi yang lebih tinggi dalam kacang kedelai dan produk kacang kedelai, seperti tahu misalnya; di sisi lain biji rami terutama mengandung lignan.

Diet estrogen bisa diambil dari berbagai produk makanan yang meliputi rempah-rempah juga; tingkat estrogen ini dapat bervariasi dari sumber ke sumber.Contoh makanan mengandung fitoestrogen tertinggi adalah biji minyak dan kacang-kacangan, dan diikuti oleh produk kedelai.

Kedelai dikategorikan sebagai penghasil isoflavon yang menyebabkan efek yang fisiologis secara alami pada tubuh.Fakta ini terbukti bahwa hanya efektif untuk mensuplai isoflavon.Jumlah untuk senyawa yang berguna dari kedelai tergantung pada jenis tanaman dan pengolahan dalam kedelai.

Flaxseed sebagai sumber fitoestrogen yang di dalamnya mengandung senyawa, seperti lignan.Relatif sangat banyak jumlah yang diperlukan; dibanding sumber-sumber lain yang lebih rendah kadungan lignannya seperti sayuran, buah-buahan dan biji-bijian.Biji rami mengandung asam alfa-linoleat dan serat larut yang berguna sebagai senyawa yang bertindak sebagai sumber fitoestrogen.

Makanan yang juga sebagai sumber fitoestrogen yang baik di sini adalah biji wijen, biji bunga matahari, chestnut, walnut, kacang pistachio.kacang tanah, almond, pistachio, hazelnut kacang Brasil dan kacang mede.

Minyak zaitun, bawang putih, kacang merah, buncis, kacang, bawang, musim dingin labu, collard hijau, brokoli, kubis, kering plum, squash musim dingin, collard hijau, tauge kacang hijau, alfalfa aprikot, peach, stroberi, raspberry, kacang hijau dan mete juga merupakan sumber makanan yang sesuai fitoestrogen.Selain dari makanan, saat ini juga telah ada obat fitoestrogen yang di sintesis, yaitu Raloxiphene. Nama dagang dari Raloxiphene adalah Evista.

Kondisi berikut dapat mengganggu Nutrisi:

  1. A.       Konsumsi alkohol berlebih – konsumsi berlebih dapat mengganggu keseimbangan kalsium dengan meningkatkan produksi hormon paratiroid dan dengan menghambat enzim-enzim yang mengubah vitamin D inaktif ke bentuk aktif; Selain itu, alkohol dapat menyebabkan defisiensi hormonal dan meningkatkan tendensi terjatuh / kecelakaan
  2. B.       Anorexia nervosa – keadaan nutrisi yang buruk, seperti pada anorexia nervosa, sebuah kelainan psikologis yang menyangkut kebiasaan makan, berasosiasi kuat dengan kehilangan tulang; faktor-faktor nutrisi dan endokrin memberikan sumbangan terhadap kehilangan tulang (khususnya kondisi estrogen rendah, yang disebabkan berat badan rendah, menyebabkan kehilangan tulang yang signifikan).

Tujuan utama rehabilitasi pada pasien-pasien osteoporosis adalah untuk mengendalikan nyeri jika fraktur sudah terjadi. Spinal compression fracture dapat menjadi sangat nyeri dan menyebabkan morbiditas yang tinggi. Analgetik oral secara reguler dapat diberikan.Modalitas yang mengurangi nyeri seperti kompres hangat dan transcutaneous electrical nerve stimulation juga dapat dipertimbangkan.Dalam periode ini, monitoring pasien untuk tanda-tanda konstipasi, retensi urin, dan depresi

 

pernapasan, yang dapat terjadi pada penggunaan analgetik narkotik, sangat penting dilakukan.

Sebuah mechanical support bagi tulang punggung dan, tergantung kasus, thoracic orthosis, dapat diberikan.Alasan utama penggunaan thoracic orthosis adalah untuk membatasi pergerakan tulang punggung.Lamanya waktu pasien harus memakai rigid spinal orthosis belum ditentukan.Namun perlu diingat bahwa imobilisasi memberikan sumbangan terhadap demineralisasi tulang.Pada periode dini mobilisasi, deep breathing exercise, penguatan pectoral dan intercostal, dan teknik-teknik konservasi punggung, semuanya dapat digunakan.

Terapi fisik berfokus pada peningkatan kekuatan pasien, fleksibilitas, postur, dan keseimbangan dalam rangka mencegah jatuh dan memaksimalkan fungsi fisiknya.Kuncinya adalah pelatihan postural.Bone  mineral density dari tulang punggung berkorelasi langsung dengan kekuatan ekstensor-ekstensor punggung; oleh karena itu, mempertahankan dan memperkuat ekstensor punggung perlu ditekankan.

Sinaki dkk menemukan bahwa menguatkan otot-otot ekstensor punggung mengurangi kifosis dan mengurangi risiko menderita vertebral compressio fracture.

Begitu regimen terapi dimulai, weight bearing exercise sebaiknya juga dimulai. Weight-bearing exercise secara reguler penting untuk menjaga massa tulang dan sebaiknya di rekomendasikan pada semua pasien, termasuk anak-anak dan remaja (untuk memperkuat kerangka saat proses maturasi). Olah raga juga meningkatkan kegesitan dan keseimbangan, sehingga mengurangi risiko terjatuh.

Olah raga aerobik, low impact, seperti berjalan dan bersepeda biasanya direkomendasikan.Saat aktivitas-aktivitas ini, pastikan bahwa pasien menjaga posisi tulang punggung tetap tegak.

Pada tahun 1984, Sinaki dan Mikkelsen menunjukkan bahwa olahraga yang menempatkan gaya fleksi pada vertebra cenderung meningkatkan jumlah fraktur vertebra pada pasien.

Pada wanita pasca menopause, impact exercise dapat meningkatkan BMD pada panggul dan tulang punggung.

Chien et al memeriksa efikasi dari program olah raga aerobik 24 minggu yang termasuk berjalan pada treadmill diikuti dengan stepping exercise pada wanita pasca menopause dengan osteopenia berusia 48  - 65 tahun. Wanita yang berolahraga mengalami peningkatan bone mineral density pada L2-L4 dan collum femur, dan juga peningkatan kekuatan quadricep, ketahanan otot, dan peak exercise oxygen consumption (VO2 max), sedangkan grup kontrol mengalami penurunan.

Selain itu, Snow et al menemukan meningkatnya BMD dari collum femur, trochanter, dan total hip pada 18 wanita pasca menopause (rata-rata usia 64 tahun), yang memakai pemberat dan ikut dalam jumping exercise 3 kali per minggu selama 32 minggu per tahun selama 5 tahun.

Hasil dari Cochrane Database of Systemic Reviews menemukan bahwa olah raga dapat mencegah kehilangan tulang dan fraktur pada wanita pasca menopause. Olah raga yang paling efektif terhadap BMD untuk collum femur bersifat non-weight bearing, high force, seperti lower limb resistance strength training, kombinasi program olah raga paling efektif untuk bone mineral density pada tulang punggung.

Walaupun berenang bukan merupakan weigthbearing exercise yang akan meningkatkan bone mineral density, ia dapat membantu ekspansi dinding dada, ekstensi spina, dan low-impact cardiopulmonary fitness. Olahraga isometrik juga sebaiknya digunakan untuk memperkuat otot-otot abdomen, membantu dalam pencegahan kifosis.

Terapi yang baik dari osteoporosis memasukkan weight-bearing exercise, 3 – 5 sesi per minggu, seperti berjalan atau jogging, dengan setiap sesi dilakukan selama 45 – 60 menit.Pasien sebaiknya diberikan instruksi program olah raga di rumah yang menggabungkan elemen-elemen yang penting untuk meningkatkan postur dan physical fitnes.

Ahli fisioterapi harus melakukan pelatihan keseimbangan, karena prevensi jatuh penting untuk mengeliminasi komplikasi fraktur. Meningkatkan keseimbangan seseorang dapat menurunkan risiko jatuh secara signifikan. Latihan keseimbangan menggabungkan penguatan dari berbagai bagian tubuh (seperti punggung, kaki), propriosepsi, dan input vestibular. Beberapa olah raga berbeda telah ditunjukkan berguna pada pasien dengan osteoporosis.

Tai Chi Chuan dan program-program fisioterapi yang spesifik terbukti efektif dalam meningkatkan keseimbangan dan mengurangi insiden terjatuh. Wolf et al memonitor 200 orang tua yang mendapatkan Tai Chi dan computerized balance training. Setelah intervensi 15 minggu, peneliti mendokumentasikan berkurangnya risiko untuk terjatuh. Tai Chi mengurangi risiko jatuh berulang sebanyak 47,5%.

Campbell et al mengamati 233 orang tua yang secara random menerima program fisioterapi yang disesuaikan per individu di rumah dibandingkan perawatan yang biasa. Peneliti menemukan bahwa setelah satu tahun, nilai rata-rata terjatuh lebih rendah pada grup olah raga daripada grup kontrol (0,87 dibandingkan 1,34). Ditambah lagi, setelah 6 bulan, subjek-subjek pada grup dengan olah raga mengalami peningkatan keseimbangan.

Tipe lain program olah raga dan latihan juga dapat secara positif mempengaruhi keseimbangan dan kekuatan. Carter et al mendemonstrasikan bahwa wanita dengan osteoporosis berusia 65 – 75 tahun yang menerima program intervensi aktivitas fisik berbasis komunitas selama 10 minggu mengalami peningkatan keseimbangan statik, keseimbangan dinamik, dan kekuatan ekstensi lutut, walaupun mereka tidak mengalami pengurangan faktor risiko terjatuh secara seginifikan.

Pelatihan dalam performa dari aktivitas kehidupan sehari-hari dan dalam penggunaan yang benar dari peralatan adaptif penting untuk mencegah terjatuh di kemudian hari.Modifikasi rumah berfokus dalam mengurangi risiko jatuh dengan memasang pegangan-pegangan pada lorong, tangga, dan kamar mandi.Penggunaan kursi saat mandi, juga dapat berguna.Aplikasi plester untuk mencegah licin dan menghindari penggunaan keset yang licin untuk meningkatkan keamanan di rumah.

 

 

Menentukan Strategi Intervensi

Terapi untuk osteoporosis pasca menopause dianggap pencegahan primer bila diberikan pada mereka yang berisiko tanpa T score dibawah -2.5 atau riwayat fragility fracture dan dianggap sebagai pengobatan bagi mereka yang sudah terdiagnosis, termasuk riwayat fraktur osteoporosis, bone mineral density yang berkurang signifikan, atau keduanya. Pemilihan regimen yang tepat bergantung pada apakah terapi didesain dengan prinsip untuk mencegah hilangnya tulang pada pasien dengan osteopenia (T score diantara -1 dan -2.5) atau untuk mengurangi kemungkinan fraktur pertama atau fraktur berikutnya pada pasien dengan osteoporosis.

Suplementasi kalsium dapat diberikan pengobatan untuk semua wanita dengan osteoporosis dan harus menjadi bagian strategi preventif untuk mengatasi berkurangnya kepadatan tulang.Peningkatan kalsium mengurangi hiperparatiroid akibat bertambahnya umur dan dapat membantu mineralisasi dari tulang yang baru terbentuk.

Analisis dari 15 penelitian intervensi kalsium pada wanita sehat dan wanita pasca menopause dengan osteoporosis memperlihatkan peningkatan hampir 2 persen pada bone mineral density tulang punggung setelah dua tahun, walaupun risiko fraktur vertebra dan nonvertebra tidak berkurang secara signifikan. Pemberian kalsium sebesar 1200 sampai 1500 mg per hari (melalui diet, suplemen, atau keduanya)direkomendasikan bagi semua wanita pasca menopause.

Vitamin D penting bagi pemeliharaan kerangka dan membantu absorpsi kalsium. Asupan vitamin ini dari diet sehari-hari merupakan masalah yang sedang berkembang, dimana sebanyak dua pertiga pasien dengan fraktur panggul digolongkan memiliki defisiensi vitamin D (didefinisikan kadar serum 25-hydroxyvitamin D [25(OH) vitamin D] di bawah 15 ng per mililiter [37,4 nmol per liter]). Orang lanjut usia dengan kondisi kronik yang hidup dengan pola assisted-living merupakan kaum yang rentan terhadap defisiensi vitamin D akibat kurangnya paparan sinar matahari.

Sebuah studi besar menunjukkan berkurangnya fraktur panggul sebanyak 33 persen diantara penduduk tempat perawatan yang diatur secara acak untuk menerima suplemen kalsium dan vitamin D, dibanding yang diberikan plasebo.

Pada penelitian lain, pengobatan dengan dosis tunggal 100.000 IU vitamin D3 setiap empat bulan mengurangi fraktur nonvertebral sampai hampir sepertiga diantara orang tua yang masih bisa jalan.

Diantara pria dan wanita di New England yang berusia tua, calcium citrate sebanyak 500 mg per hari dan vitamin D3 sebanyak 700 IU per hari mengurangi risiko fraktur nonvertebra.

Ada bukti kuat bahwa suplementasi vitamin D meningkatkan kekuatan otot dan mengurangi risiko jatuh. Tabel berikut menunjukkan berbagai bentuk suplemen kalsium dan vitamin D.

 

Suplementasi Kalsium dan Vitamin D

 

Rekomendasi bagi pasien-pasien dengan osteoporosis termasuk dosis harian 400-800 IU vitamin D dan 1200 – 1500 mg kalsium. Wanita premenopausal dan pria kurang dari 50 tahun tanpa faktor risiko untuk osteoporosis sebaiknya mendapat total 1000 mg kalsium setiap harinya. Wanita pasca menopause dan pria lebih dari 50 tahun, dan orang lain yang berisiko osteoporosis sebaiknya mendapat 1200 – 1500 mg kalsium setiap harinya. Sumber kalsium yang bagus termasuk produk susu, sarden, kacang-kacangan, biji bunga matahari, tahu, sayur-sayuran seperti daun lobak dan makanan dengan fortifikasi seperti jus jeruk.

Orang tua lebih dari 50 tahun sebaiknya mendapat 400 – 800 IU vitamin D3 setiap harinya. Semua orang dewasa lebih dari 50 tahun sebaiknya menerima 800 – 1000 IU vitamin D3 setiap hari. Sumber baik vitamin D termasuk telur, hati, butter, ikan berlemak, dan makanan dengan fortifikasi seperti jus jeruk.

Sebuah meta-analisis dari 12 double blind, randomized, controlled trial (RCT) untuk fraktur non vertebral dan 8 RCT untuk fraktur panggul yang membandingkan vitamin D oral (dengan atau tanpa kalsium) dengan kalsium sendiri atau plasebo menemukan bahwa pencegahan fraktur non vertebral dengan vitamin D bergantung pada dosis dan dosis lebih tinggi mengurangi fraktur sebanyak sedikitnya 20% bagi individu berusia 65 tahun atau lebih.

Kebiasaan merokok dan minum alkohol berlebihan harus dihentikan. Keduanya dihubungkan dengan risiko fraktur yang lebih besar.

Tirah baring atau imobilitas akibat penyebab lain dapat menyebabkan hilangnya tulang secara cepat. Selain itu, kejadian terjatuh dan persentase jatuh yang menyebabkan fraktur meningkat seiring dengan umur.

Meta-analisis menunjukkan latihan kekuatan otot, latihan keseimbangan, penilaian lingkungan rumah terhadap risiko atau bahaya, penghentian pengobatan psikotropika, dan penggunaan program multidisiplin untuk menilai faktor risiko, semuanya membantu mengurangi kejadian terjatuh.

Pendekatan lain adalah dengan mengenakan hip protector untuk mengurangi trauma saat terjatuh; walaupun kepatuhan pasien terhadap strategi ini biasanya buruk, jika digunakan dengan benar, strategi ini dilaporkan mengurangi risiko fraktur panggul. Aktivitas fisik secara rutin, termasuk aerobik, angkat berat, dan latihan ketahanan, efektif dalam meningkatkan bone mineral density dari tulang punggung dan memperkuat massa otot pada wanita pasca menopause, namun tidak ada penelitian besar yang menunjukkan bahwa intervensi ini mengurangi risiko fraktur.

Banyak bukti menunjukkan bahwa program intervensi yang agresif dapat mengurangi risiko fraktur dan meningkatkan kualitas hidup diantara wanita pasca menopause dengan osteoporosis. Beberapa pilihan farmakologi tersedia, dan dapat digolongkan menurut mekanisme kerjanya. Dua kelas utama obat yang digunakan untuk mengobati osteoporosis adalah agen antiresorptif (agen yang menghambat resorpsi tulang dengan menghambat aktivitas osteoclast) dan agen anabolik (agen yang menstimulasi pembentukan tulang dengan bekerja terutama pada osteoblast). Tabel berikut menunjukkan obat-obat yang sudah disetujui Food and Drug Administration.

 

Pilihan Farmakologi Untuk Osteoporosis

 

v  Agen Antiresorptif

Dengan menghambat aktivitas osteoclast, agen antiresorptif memperlambat siklus remodeling, sehingga membantu mineralisasi dari matriks tulang dan secara potensial menstabilkan mikroarsitektur trabekular. Agen-agen ini meningkatkan bone mineral density pada wanita dengan osteopenia atau osteoporosis dan mengurangi risiko fraktur pada wanita dengan osteoporosis, walaupun efikasi berbeda-beda diantara agen.

v  Postmenopausal Hormone-Replacement Therapy

Hormone-replacement therapy dulu dianggap terapi primer untuk wanita pasca menopause dengan osteoporosis.Estrogen menghambat resorpsi tulang dengan menghambat signal sitokin pada osteoclast, meningkatkan bone mineral density, dan mengurangi insiden fraktur vertebra baru sampai hampir 50 persen. Pengobatan dengan estrogen terkonjugasi dosis rendah (0,3 atau 0,45 mg per hari)atau dosis sangat rendah dari estradiol (0,014 mg per hari) juga meningkatkan bone mineral density, namun efikasi dari efek anti-fraktur dari terapi ini belum ditegakkan.

Diantara wanita pada Women’s Health Initiative trial, dimana mereka secara acak menerima estrogen terkonjugasi, dengan atau tanpa progestin, penurunan fraktur panggul sebesar 33 persen.Penghentian konsumsi estrogen menyebabkan kehilangan tulang yang dapat diukur, namun tidak pasti apakah penghentian ini menyebabkan risiko fraktur yang lebih besar daripada yang melanjutkan pengobatan.Kekhawatiran baru-baru ini mengenai risiko nonskeletal dari penggunaan estrogen jangka panjang (termasuk risiko kanker payudara, ca cervix, ca uterus, dan risiko penyakit kardiovaskular), ditambah dengan adanya obat-obat lain untuk mengobati osteoporosis telah mengurangi entusiasme untuk menggunakan hormone-replacement therapy pada pengobatan dan pencegahan osteoporosis.

v  Selective Estrogen-Receptor Modulators

Modulator reseptor estrogen yang selektif seperti raloxifene menghambat resorpsi tulang melalui mekanisme yang sama seperti estrogen. Raloxifene sedikit meningkatkan bone mineral density dari tulang punggung dan mengurangi risiko fraktur vertebra sebesar 40 persen pada wanita dengan osteoporosis, namun tidak memiliki efek pada risiko fraktur nonvertebra. Risiko kanker payudara berkurang dengan penggunaan jangka panjang raloxifene, namun obat ini belum disetujui untuk digunakan pada indikasi ini. Obat baru golongan selective estrogen-receptor modulator sedang dalam phase 2 dan phase 3 clinical trial.Nama obat Selective Estrogen Receptor Modulator (Raloxifene) yang sudah ada di pasaran adalah Evista.

v  Bisphosphonate

Bisphosphonate adalah agen antiresorptive yang paling banyak diresepkan dan seringkali dianggap first-line therapy untuk pengobatan osteoporosis pasca menopause.Agen-agen ini menghambat resorpsi dengan menghambat perlekatan osteoclast pada matriks tulang dan membantu kematian sel terprogram (apoptosis).Bisphosphonate generasi pertama termasuk etidronate dan clodronate; keduanya tidak disetujui untuk pengobatan osteoporosis.Alendronate dan risedronate, dua obat bisphosphonate generasi kedua yang mengandung nitrogen, terbukti meningkatkan bone mineral density pada wanita pasca menopause dengan osteopenia atau osteoporosis; pada wanita dengan osteoporosis, obat-obat ini mengurangi insiden fraktur panggul, vertebra, dan nonvertebra sampai hampir 50 persen, terutama saat tahun pertama pengobatan.Seperti halnya obat antiresorptif lainnya, peningkatan bone mineral density karena alendronate atau risedronate menyebabkan efek antifraktur.Sehingga, pengukuran berikutnya dengan dual-energy x-ray absorptiometry dapat terlihat tidak sebanding dengan pengurangan risiko fraktur yang dihasilkan.

Data-data menunjukkan alendronate dapat diberikan dan aman untuk setidaknya tujuh tahun tanpa pengaruh buruk terhadap kekuatan tulang. Ditambah lagi, penghentian dari terapi alendronate jangka panjang (lima tahun atau lebih) menyebabkan berkurangnya tulang (minimal) dalam tiga sampai lima tahun berikutnya. Alendronate atau risedronate yang digunakan seminggu sekali terlihat mengurangi tingkat esophagitis yang diinduksi obat, dibandingkan dengan dosis tiap hari.

Pada studi berikutnya, alendronate meningkatkan bone mineral density dari tulang punggung dan panggul sedikit lebih banyak dari risedronate, walaupun relevansi klinik dari penemuan ini belum pasti.

Bisphosphonate lainnya masih belum resmi atau masih diteliti untuk pengobatan osteoporosis. Pamidronate intravena telah digunakan untuk mengobati wanita yang tidak dapat menggunakan bisphosphonate oral; namun, efikasinya dalam mengurangi fraktur belum diteliti. Reaksi hipersensitivitas akut dan lanjut dapat terjadi pada penggunaan pamidronate intravena, dan penggunaannya merupakan kontraindikasi pada pasien dengan defisiensi vitamin D, karena obat ini dapat menyebabkan penurunan kadar kalsium serum dengan cepat.

Pada 2005, ibandronate tampak menurunkan insiden fraktur vertebra pada wanita dengan osteoporosis secara signifikan dan mengurangi insiden fraktur nonvertebra pada wanita dengan osteoporosis signifikan (T score dibawah -3.0).

Zoledronate intravena disetujui untuk pengobatan hiperkalsemia malignan, multiple myeloma, dan metastase tulang, dapat menekan resorpsi tulang dan meningkatkan bone mineral density pada wanita pasca menopause selama satu tahun setelah dosis tunggal 4 mg. Obat ini sedang dalam phase three trial untuk evaluasi tingkat keamanan dan efikasi obat ini dalam mengurangi fraktur osteoporosis.

Ada beberapa obat golongan bisphosphonate yang sudah ada di pasaran. Alendronate sodium dipasarkan dengan nama Fosamax. Risedronate dijual sebagai Actonel.Bonviva merupakan obat dengan zat aktif ibandronic acid.Selain itu terdapat Reclast, yang isinya Zoledronic acid.

v  Calcitonin

Calcitonin adalah sebuah peptida endogen yang menginhibisi aktivitas osteoclast secara parsial.Calcitonin nasal dan subkutan disetujui untuk pengobatan osteoporosis pasca menopause.

Walaupun pengobatan wanita dengan osteoporosis dengan calcitonin nasal sebesar 200 IU per hari tampak mengurangi insiden fraktur vertebral (namun bukan nonvertebral)pada sebuah penelitian, kesalahan metodologi pada studi tersebut mengurangi kepercayaan klinisi untuk menggunakan agen ini.

Pada sebuah studi dengan perbandingan plasebo, calcitonin nasal mengurangi nyeri akibat fraktur tulang punggung baru, walaupun sekarang lebih dipilih untuk mengobati osteoporosis dengan agen yang lebih poten dan melakukan manajemen nyeri dengan obat terpisah.

Nama paten obat ini di pasaran ialah Miacalcin dan Fortical.

v  Strontium Ranelate

Strontium ranelate diberikan secara oral dan menstimulasi calcium uptake pada tulang dan pada saat yang sama menginhibisi resorpsi tulang. Pada sebuah trial wanita pascamenopause dengan osteoporosis, strontium ranelate yang diberikan setiap hari mengurangi risiko fraktur vertebra sampai 40 persen. Namun, reduksi signifikan fraktur nonvertebra hanya ditemukan pada subgrup kecil wanita. Obat ini sudah diberikan ijin agensi regulasi Eropa, namun belum diberi ijin FDA.

Obat ini digunakan sebagai anti-osteoporosis dan dipasarkan dengan nama Protos.

v  Agen Anabolik

Obat anabolik dini adalah sodium fluoride, yang digunakan pada sekitar 1970 dan 1980 karena kemampuan menstimulasi pembentukan tulang baru. Namun, sebuah trial pada 1990 menemukan bahwa meskipun terdapat peningkatan dramatis bone mineral density, risiko fraktur nonvertebral sebenarnya meningkat dengan penggunaan fluoride. Pada tahun 2002, hormon paratiroid (1-34( sintetik (teriparatide) merupakan agen anabolik pertama yang diijinkan FDA untuk pengobatan osteoporosis pasca menopause. Tidak seperti agen-agen antiresorptif, hormon paratiroid memacu remodeling tulang dengan meningkatkan pembentukan tulang.

Pada sebuah penelitian besar yang melibatkan wanita pasca menopause dengan osteoporosis, 20 ug hormon paratiroid per hari yang diberikan secara subkutan meningkatkan bone mineral density secara bermakna dan mengurangi fraktur vertebral dan non vertebral sebanyak lebih dari 50 persen. Namun, penelitian ini dihentikan setelah 20 bulan karena kekhawatiran terhadap terbentuknya osteosarkoma pada tikus-tikus yang diiobati dengan hormon paratiroid (1-34) dosis tinggi.Namun, studi retrospektif tidak menemukan asosiasi antara osteosarkoma dan hiperparatiroidisme primer atau sekunder pada manusia, dan tidak ada kasus osteosarkoma pada dilaporkan pada lebih dari 200.000 pasien yang diobati dengan hormon paratiroid.Rekomendasi saat ini adalah terapi hormon paratiroid sebaiknya dibatasi pada orang-orang dengan osteoporosis sedang sampai berat dan durasi terapi tidak melebihi dua tahun. Hormon paratiroid (1-34) di toleransi dengan baik, walaupun kadang-kadang terjadi hiperkalsemia ringan yang asimptomatis (kadar kalsium serum antara 10,5 dan 11,0 mg per dL [2,6 dan 2,8 mmol per liter]). Biaya dan rute pemberian subkutan merupakan faktor utama yang membatasi penggunaannya.

Teriparatide dijual di pasaran dengan label Forteo.

v  Agen Biologis dan Imunologis

Antibodi monoklonal yang mencegah pembentukan osteoclast, yang menyebabkan berkurangnya pembongkaran tulang dan meningkatkan massa tulang, memberikan hasil yang efektif dalam mengobati osteoporosis. Antibodi monoklonal terikat pada reseptor aktivator dari nuclear factor-kappa B ligand (RANKL), merupakan transmembrane atau soluble protein penting untuk pembentukan, fungsi, dan ketahanan hidup osteoclast, sel yang bertanggung jawab untuk resorpsi tulang. Obat ini dapat mencegah fraktur pada wanita pasca menopause dengan osteoporosis dan risiko fraktur yang tinggi (riwayat fraktur osteoporosis, gagal dengan pengobatan lain).

Obat ini dijual dengan nama Prolia (zat aktif Denosumab).

v  Terapi Kombinasi

Walaupun studi-studi telah memberikan sugesti bahwa menggabungkan agen-agen antiresorptif dapat sedikit meningkatkan bone mineral density bila dibandingkan dengan monoterapi, tidak ada data yang meng-indikasikan bahwa terapi kombinasi lebih superior untuk mengurangi risiko fraktur. Juga tidak ada bukti bahwa mengkombinasi hormon paratiroid dengan sebuah obat antiresorptif memberikan hasil additif atau efek sinergistik, namun penggunaan hormon paratiroid siklik (contohnya paratiroid setip hari selama 3 bulan diikuti dengan penghentian pengobatan selama 3 bulan untuk periode 15 bulan) dengan alendronate mungkin sama efektif dengan hormon paratiroid setiap hari dengan alendronate. Walaupun begitu, kehilangan tulang akan terjadi setelah penghentian hormon paratiroid, namun dapat dicegah jika terapi ini diikuti dengan pengobatan dengan obat antiresorptif seperti alendronate.

 

Rekomendasi Yang Ada Saat Ini

Waktu optimal dan tipe terapi preventif masih belum ditetapkan secara jelas. Banyak wanita pasca menopause memiliki T score diantara -1,0 dan -2,5 namun tidak ada faktor risiko lain.

Postmenopausal hormon replacement therapy, yang dahulu dianggap pendekatan preventif terbaik bagi wanita-wanita ini, tidak lagi direkomendasikan akibat risiko yang dilaporkan pada Women’s Health Initiative trial.

Bisphosphonate mencegah kehilangan tulang pada wanita dengan osteopenia dan dapat digunakan sebagai profilaksis, namun masalah harga dan kekhawatiran mengenai efek pada mineralisasi kerangka dalam jangka panjang merupakan faktor-faktor yang membatasi penggunaannya.

Hal lain yang masih perlu dipikirkan adalah perawatan yang tepat untuk pasien-pasien yang tetap mengalami fraktur walaupun diberikan intervensi farmakologi yang agresif. Apakah agen-agen baru seperti antibodi sintetik pada aktivator reseptor dari nuclear factor-kB ligand (AMG 162) atau strontium ranelate akan efektif dalam mencegah fraktur baru pada pasien-pasien itu perlu diteliti.

Terdapat kontroversi mengenai penggunaan vertebroplasty atau kyphoplasty, prosedur yang memasukkan material untuk memperluas vertebra yang mengalami kompresi dan mengurangi nyeri yang disebabkan oleh fraktur baru.Hal ini dikarenakan kurangnya percobaan placebo-kontrol dan kekhawatiran mengenai kekuatan mekanik dari vertebra di dekatnya setelah prosedur ini.Ini menyebabkan  rekomendasi penggunaannya masih terbatas.

Beberapa profesional dan agensi pemerintah telah menyediakan guideline untuk pengobatan.

 

Guideline Terapi Postmenopausal Osteoporosis

Anamnesis yang baik dan pemeriksaan fisik yang mencakup faktor-faktor risiko atau tanda-tanda osteoporosis (khususnya fraktur fragilitas sebelumnya, berkurangnya tinggi badan, atau keduanya, dan kemungkinan penyebab sekunder kehilangan tulang) yang dikombinasi dengan pengukuran bone mineral density sebaiknya memandu keputusan terapi. Mengingat tingginya prevalensi kadar yang rendah dari 25(OH) vitamin D pada wanita dengan osteoporosis, pengukuran kadar serum 25(OH) vitamin D oleh laboratorium yang terpercaya sebaiknya dilakukan.

 

 

BAB 6 – KESIMPULAN

Tulang merupakan bagian yang sangat penting bagi manusia.Tulang berperan untuk pergerakan, ketahanan tubuh, mengerjakan aktivitas sehari-hari secara normal, bekerja, maupun rekreasi. Osteoporosis merupakan penyakit yang menyerang tulang, dan menyebabkan berkurangnya kekuatan tulang. Komplikasi utama dari osteoporosis adalah fraktur, yang sangat sering terjadi bila osteoporosis tidak ditangani dengan baik.Fraktur merupakan masalah yang serius karena menyebabkan nyeri yang hebat dan dapat menyebabkan disabilitas permanen.

Kemajuan teknologi telah menyebabkan kita mengetahui jauh lebih banyak hal mengenai osteoporosis. Mulai dari etiologi, patofisiologi, cara diagnosis, dan terapi. Kemajuan di bidang biomolekuler menyebabkan kita lebih mengerti mengenai perjalanan penyakit osteoporosis. Molekul-molekul yang bertanggung jawab mulai ditemukan, dan mungkin saja dapat digunakan untuk target pengobatan di kemudian hari. Alat-alat baru ditemukan, dan dapat digunakan untuk mendiagnosa osteoporosis. Pemahaman yang lebih baik terhadap perjalanan osteoporosis membuka pengetahuan mengenai upaya untuk mencegah terjadinya osteoporosis. Untuk diagnosis, DXA merupakan alat yang saat ini banyak digunakan dan dapat mendiagnosa osteoporosis dengan baik.

Pada osteoporosis terdapat berbagai aspek dan modalitas terapi. Anamnesis yang baik dan pemeriksaan fisik yang mencakup faktor-faktor risiko atau tanda-tanda osteoporosis (khususnya fraktur fragilitas sebelumnya, berkurangnya tinggi badan, atau keduanya, dan kemungkinan penyebab sekunder kehilangan tulang) yang dikombinasi dengan pengukuran bone mineral density sebaiknya memandu keputusan terapi. Terapi non-farmakologi merpakan bagian penting dari penanganan osteoporosis.

 

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53.     Iwamoto J, Takeda T, Ichimura S. Effect of exercise training and detraining on bone mineral density in postmenopausal women with osteoporosis. J Orthop Sci. 2001;6(2):128-32.
54.     Wolf SL, Barnhart HX, Kutner NG, McNeely E, Coogler C, Xu T. Reducing frailty and falls in older persons: an investigation of Tai Chi and computerized balance training. Atlanta FICSIT Group. Frailty and Injuries: Cooperative Studies of Intervention Techniques. J Am Geriatr Soc. May 1996;44(5):489-97.
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