ABSTRAK

Osteoporosis is a chronic disease characterized by reduced bone mass. Factors

which affect such as family history, physical activity, nutritional status and habits of high
calcium foods.Objective. To analyze the correlation between family history, physical activity,
nutritional status and habits of high calcium foods consumption with bone density at
postmenopausal women.

Osteoporosis merupakan penyakit kronik yang ditandai dengan

pengurangan massa tulang. Faktor yang berpengaruh antara lain riwayat keluarga, aktifitas
fisik, status gizi dan kebiasaan mengkonsumsi makanan berkalsium tinggi.Tujuan:
Mengetahui hubungan antara riwayat keluarga, aktifitas fisik, status gizi dan kebiasaan
mengkonsumsi makanan berkalsium tinggi dengan kepadatan tulang pada wanita
postmenopause. Osteoporosis lebih banyak terjadi pada wanita daripada pria.

Hal ini
disebabkan pengaruh hormon estrogen yang mulai menurun kadarnya dalam
tubuh sejak usia 35 tahun sedangkan pada pria hormon testoteron turun
pada usia
65 tahun. Menurut statistik dunia 1 dari 3 wanita rentan terkena penyakit
osteoporosis [3].
Insiden osteoporosis meningkat sejalan dengan meningkatnya populasi
usia lanjut[2]. Pada tahun 2005 terdapat 18 juta lanjut usia di Indonesia,
jumlah ini
akan bertambah hingga 33 juta pada tahun 2020 dengan usia harapan hidup
mencapai 70 tahun[4].

ISI
CURRENTLY APPROVED MEDICATIONS

Bisphosphonates are mainstays of therapy for osteoporosis. Four are currently FDA
approved for the treatment of osteoporosis: alendronate, risedronate, ibandronate, and
zoledronic acid (Table 2).10-13Bisphosphonates bind to hydroxyapatite and block the enzyme
farnesyl pyrophosphate synthase in bone tissue and inhibit osteoclast-mediated bone
resorption.10-13 Alendronate, risedronate, and ibandronate are all available as both daily and
intermittent (weekly or monthly) dosage forms.10-12Zoledronic acid is administered as an
annual intravenous infusion.13 The most common side effects with oral bisphosphonates are
gastrointestinal (GI) side effects, generally esophageal irritation or heartburn. 10-12 These
effects, along with the very low bioavailability, contribute to the specific and detailed patient
administration instructions (Table 2).10-13 Zoledronic acid has GI side effects similar to
placebo, but is associated with myalgias, fever, and headache. Serum creatinine should be
assessed before and after use of zoledronic acid due to reports of renal failure after
treatment.13 All bisphosphonates are not recommended for use with renal dysfunction. 1013
Intermittent dosing of bisphosphonates (weekly and monthly) may decrease risk of
administration-related adverse effects.

Table 2 Bisphosphonate dosage

The bisphosphonates both improve BMD and also reduce the incidence of hip and
nonvertebral fractures. In 2008 investigators evaluated the effect of alendronate on primary
and secondary prevention of osteoporosis in postmenopausal women. 14 The review

analyzed data from 11 trials with a total patient population of more than 12,000 women.
Alendronate 10 mg daily resulted in a significant 45% relative reduction in primary and
secondary prevention of vertebral fractures.14 Only secondary prevention of hip fractures
was statistically significant, however, with a relative reduction of 53%. A similar review
evaluated risedronate, combining 7 trials and just over 14,000 women. Similar to
alendronate, risedronate 5 mg daily provided a significant effect on secondary prevention of
both vertebral and hip fractures, reducing the relative risk 39% and 26%, respectively. 15 A
meta-analysis of ibandronate indicated that the monthly dosage reduces the relative risk of
nonvertebral fractures by 38% to 43%.16Zoledronic acid has demonstrated a 27% relative
reduction in the incidence of new nonvertebral fractures when administered within 3 months
of a hip fracture.17
Calcitonin-salmon is also an antiresorptive therapy for osteoporosis, and affects
BMD by inhibiting the activity of osteoclasts. It is available in a non-oral (nasal
spray) formulation for the treatment of osteoporosis. It should be administered
daily in alternating nostrils. Common side effects are local, and include nasal
irritation and occasionally epistaxis.18
Calcitonin has demonstrated positive effects on spinal BMD, but has not been
shown to significantly affect hip BMD. The Prevent Recurrence of Osteoporotic
Fractures (PROOF) study in 2000 was a landmark multicenter clinical trial for
calcitonin.19 The population of the trial was more than 1,200 subjects randomly
assigned to calcitonin or placebo for 5 years. At the conclusion of the PROOF
study, a 36% relative risk reduction in vertebral fractures was noted. Also in
2000, a review was undertaken to analyze the impact of calcitonin on
corticosteroid-induced osteoporosis, including data from 9 trials and 221
patients.20 Results were not dramatic, with calcitonin showing a 3% improvement
(over placebo) in lumbar BMD. No fracture data were reported in this review. In
addition to its effects on spinal BMD, calcitonin has been shown to alleviate pain
from vertebral osteoporotic compression fractures. The mechanism of calcitoninproduced analgesia remains unclear, but it has been proposed to include beta
endorphins and prostaglandins.21
Raloxifene is a selective estrogen receptor modulator (SERM). It antagonizes
estrogen receptors in some tissues and agonizes estrogen receptors at other
tissues, such as bone tissue. Estrogen affects the balance of osteoclast and
osteoblast activity, and its deficiency is associated with an increase in
osteoclastic activity. Raloxifene is administered as a once-daily oral formulation.
Side effects include hot flashes, especially during the first 6 months of therapy.
Raloxifene has been associated with an increase in thromboembolic events, and

carries a black box warning about this risk.22 The Multiple Outcomes of
Raloxifene Evaluation (MORE) study evaluated raloxifene versus placebo in
nearly 8,000 women for 3 years with a 1-year extension. 23 Results from the
MORE study included a 55% relative risk reduction in first vertebral fractures
and a 30% relative risk reduction in secondary vertebral fractures. 22
Teriparatide is parathyroid hormone produced using recombinant DNA
technology. Teriparatide has anabolic effects on bone, stimulating the activity of
osteoblasts. It is administered as a once-daily subcutaneous injection. Side
effects include orthostatic hypotension, nausea, myalgia, and arthralgia.
Teriparatide has a black box warning regarding risk of osteosarcoma.
Osteosarcoma was observed in rats exposed to teriparatide at doses much
higher than the currently approved dose.24 A study of more than 1,600 women
randomly assigned to daily subcutaneous teriparatide or placebo reported a
53% relative risk reduction in nonvertebral fragility fractures. 25 Teriparatide is not
recommended for use beyond 2 years due to lack of safety and efficacy data.
After 2 years, some studies suggest that the addition of bisphosphonates helps
continue increase in BMD or helps maintain BMD gained during teriparatide
treatment.26
Denosumab, an antiresorptive therapy, prevents the activation of receptor
activator of nuclear factor kappa B ligand (RANKL) receptors on the surface of
osteoclasts. The RANK receptor plays a role in formation, function, and survival
of osteoclasts. Denosumab is administered by a healthcare professional as a
twice-yearly subcutaneous injection. The most commonly reported side effects
include back and musculoskeletal pain, pain in extremity, cystitis, and
hypercholesterolemia. Serious reported side effects include serious infections
and osteonecrosis of the jaw (ONJ). Patients at risk of infection (including
patients on immunosuppressive therapy) should have a risk-benefit evaluation
prior to considering denosumab therapy.27 Denosumab improves BMD and
decreases fractures. A study of nearly 8,000 osteoporotic women randomized to
denosumab or placebo revealed a 68% relative risk reduction in vertebral
fractures and a 40% relative risk reduction in hip fractures. 28
No head-to-head comparative trials exist to guide selection of osteoporosis
therapy for a specific patient. Of the guidelines discussed previously, there is
discordance on which therapies are used as first-line treatment (Table 1). 4,6-8 The
NOF guidelines simply list the agents that have been approved for osteoporosis
treatment.6 AACE indicates that alendronate, risedronate, zoledronic acid, and

denosumab are considered first-line therapy due to their proven efficacy against
fractures. The AACE guidelines do not offer any recommendations for choosing
between these 4 agents.4 The NAMS and ACR guidelines recommend use of
bisphosphonates as first-line therapy, but offer no suggestion on choosing a
specific bisphosphonate.7,8 Practitioners must rely on their own analysis of
efficacy, safety, and cost when deciding between currently available therapies.