Saturday, 9 May 2020

treatment of osteoporosis, its diagnosis and drugs tom prevent fracture


Q.1: What are the risk factors for osteoporotic fracture?  Ans: The risk factors for osteoporotic fracture include (but are not limited to)  1)  increasing age, 2) female sex, 3) postmenopausal women, 4) hypogonadism or premature ovarian failure,5)  low body weight,6) history of parental hip fracture, 7) ethnic background (white persons are at higher risk than black persons), 8) previous clinical or morphometric vertebral fracture,9)  previous fracture due to minimal trauma (that is, previous osteoporotic fracture), 10) rheumatoid arthritis, 11) current smoking, 12) alcohol intake (3 or more drinks daily), 15( low bone mineral density (BMD),16)  vitamin D deficiency, 17) low calcium intake, 18) hyperkyphosis, 19)  falling, and 20) immobilization . Another risk factor for osteoporotic fracture is 21) long-term use of certain medications, the most commonly implicated being glucocorticoids, anticoagulants, anticonvulsants, aromatase inhibitors, cancer chemotherapeutic drugs, and gonadotropin-releasing hormone agonists
(Courtsey: CLINICAL GUIDELINES |9 MAY 2017
;-Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update from the American College of Physicians FREE
Amir Qaseem, MD, PhD, MHA; Mary Ann Forciea, MD; Robert M. McLean, MD; Thomas D. Denberg, MD, PhD; for the Clinical Guidelines Committee of the American College of Physicians (*))




Osteoporotic fracture:  Q.2: How to diagnose osteoporosis?? Osteoporosis can be diagnosed by the occurrence of fragility fracture. In patients without fragility fracture, osteoporosis is often diagnosed by low BMD.
Q. 2A: DXA : Method A:--DXA:  Dual-energy x-ray absorptiometry (DXA) is the current gold standard test for diagnosing osteoporosis in people without an osteoporotic fracture. Results of DXA are scored as SDs from a young, healthy norm (usually female) and reported as T scores.

For example, a T score of –2 indicates a BMD that is 2 SDs below the comparative norm. The international reference standard for the description of osteoporosis in postmenopausal women and in men aged 50 years or older is a femoral neck BMD of 2.5 SD or more below the young female adult mean .
Low BMD as measured by DXA is an imperfect predictor of fracture risk, identifying less than one half of the people who go on to have an osteoporotic fracture.
Q. 3:  Z score?? Method B:- Bone density can also be classified according to the Z score, the number of SD above or below the expected BMD for the patient's age and sex.
Z score of –2.0 or lower is defined as either “low BMD for chronological age” or “below the expected range for age,” and those above –2.0 are “within the expected range for age” .

Q, 4: What is FRAX??  Risk scores that combine clinical risk factors with BMD testing results, such as FRAX (the World Health Organization Fracture Risk Assessment Tool), can be used to predict fracture risk among people with low bone density.
Q. 5. What drug and how long to treat?? ACP recommends that clinicians offer pharmacologic treatment with A) alendronate, B) risedronate, C) zoledronic acid, or D) denosumab to reduce the risk for hip and vertebral fractures in women who have known osteoporosis. (Grade: strong recommendation; high-quality evidence) ACP recommends that clinicians treat osteoporotic women with pharmacologic therapy for 5 year as per American College of Physicians (ACP)


ACP (American College of Physicians )
This guideline focuses on the comparative benefits and risks of short- and long-term pharmacologic treatments for low bone density, including pharmaceutical prescriptions, calcium, vitamin D, and estrogen.  Men and women with low bone density and osteoporosis. ACP recommends that clinicians should make the decision whether to treat osteopenic women 65 years of age or older who are at a high risk for fracture based on a discussion of patient preferences, fracture risk profile, and benefits, harms, and costs of medications. Q. 5A: What drugs?? osteoporosis include A) bisphosphonates (alendronate, risedronate, ibandronate, zoledronic acid), B) peptide hormones (teriparatide [ 1,3,4 amino acid fragment of parathyroid hormone] and calcitonin), C) estrogen (in the form of menopausal hormone therapy) for postmenopausal women, and D) selective estrogen receptor modulators (SERMs) (raloxifene for postmenopausal women).

 Q. 5B: What is most current and promising agent/ drugs?? Most of the treatments aim to prevent bone resorption. E)  Denosumab (a new biologic agent), dietary and supplemental calcium, and vitamin D are also used for treatment. F) Bazedoxifene, a SERM, has recently been approved by the U.S. Food and Drug Administration (FDA) with conjugated estrogen for prevention of osteoporosis.



Q. 6: What is  meant  by  Osteoporosis?? Osteoporosis is a systemic skeletal disease characterized by decreasing bone mass and microarchitectural deterioration of bone tissue that leads to an increased risk for bone fragility and fracture. Although osteoporosis can be present in any bone, the hip, spine, and wrist are most likely to be affected.
 Q. 7 : Prevalence of osteoprosis: Osteoporosis is found in an estimated 200 million people worldwide and an estimated 54 million men and women in the United States have osteoporosis or low bone density .Approximately 50% of Americans older than 50 years are at risk for osteoporotic fracture .

Q. 8: What changes have bn made recently by FDA on drug treatment of osteoporosis?? Pharmacologic treatments for osteoporosis include bisphosphonates (alendronate, risedronate, ibandronate, zoledronic acid), peptide hormones (teriparatide [the 1,3,4 amino acid fragment of parathyroid hormone] and calcitonin), estrogen (in the form of menopausal hormone therapy) for postmenopausal women, and selective estrogen receptor modulators (SERMs) (raloxifene for postmenopausal women). Most of the treatments aim to prevent bone resorption.

Denosumab (a new biologic agent), dietary and supplemental calcium, and vitamin D are also used for treatment. Bazedoxifene, a SERM, has recently been approved by the U.S. Food and Drug Administration (FDA) with conjugated estrogen for prevention of osteoporosis.
Q.9:- Do we know that  FDA do not approve etidronate and pamidronate     ??     Etidronate and pamidronate,” neither of which are FDA-approved for the prevention of fractures or treatment of osteoporosis. This is as per      Several therapies included in the 2008 guideline have been excluded

Several therapies included in the 2008 guideline have been excluded from the update, including calcitonin, which is no longer widely used for osteoporosis treatment, and both etidronate and pamidronate, neither of which are FDA-approved for the prevention of fractures or treatment of osteoporosis.

Q.10 what is then the moist premising agent?? One new biologic, denosumab, a human monoclonal antibody approved by the FDA for treatment of osteoporosis, has been added since publication of the 2008 guideline. Different medications for the treatment of osteoporosis may affect various parts of the skeletal system differently. This guideline is endorsed by the American Academy of Family Physicians.
Q.11. Who helpful is Bisphosphonates (alendronate , risedronate , and zoledronic acid) ? ,
High-quality evidence showed that bisphosphonates, including alendronate , risedronate , and zoledronic acid , reduce vertebral, nonvertebral, and hip fractures compared with placebo in postmenopausal osteoporotic women. High-quality evidence also showed that ibandronate reduces the risk for radiographic vertebral fractures, although evidence is insufficient to determine the effect of ibandronate on hip fractures .Moderate-quality evidence showed that zoledronic acid reduces radiographic vertebral fractures in osteoporotic men
Q.12:  How useful is Denosumab???
High-quality evidence showed that treatment with denosumab reduces radiographic vertebral, nonvertebral, and hip fractures compared with placebo in postmenopausal osteoporotic women (96–108). One Japanese trial and its 1-year open-label extension study included postmenopausal osteoporotic women with prevalent radiographic vertebral fractures and showed that denosumab protected against radiographic vertebral fractures (101, 109).
Q.12:  How useful is Teriparatide??
High-quality evidence showed that treatment with teriparatide reduces radiographic vertebral and nonvertebral fractures compared with placebo in postmenopausal osteoporotic women
Q.12:  How useful is SERMs??
High-quality evidence showed that raloxifene reduces vertebral fractures in osteoporotic women; however, it did not statistically significantly decrease the risk for nonvertebral or hip fractures compared with placebo
 How useful is Bazedoxifene?? Bazedoxifene is FDA-approved in combination with conjugated estrogens for the prevention of osteoporosis (20 mg, with 0.45 mg conjugated estrogen). The systematic review did not find any randomized controlled trials (RCTs) with this combination that had primary fracture outcomes.
 Q. 13. How useful is Estrogen Therapy for Postmenopausal Women in fracture prevention??
Moderate-quality evidence showed no difference in reduced fracture with estrogen treatment in postmenopausal women with established osteoporosis This differs from the 2008 guideline, which reported high-quality evidence that estrogen therapy was associated with reduced risk for vertebral, nonvertebral, and hip fractures in postmenopausal women Studies included in the 2008 guideline focused on postmenopausal women or those with low bone density as opposed to the newer data, which focused on postmenopausal women with established osteoporosis.
Q.14: How useful is Calcium or Vitamin D??
Moderate-quality evidence showed that the overall effect of calcium or vitamin D alone on fracture risk is uncertain. Studies showed no difference between calcium alone and placebo for reduced vertebral and nonvertebral fracture risk although adherence was low. Data on the efficacy of vitamin D alone for reducing fracture risk are mixed, and the overall effect is uncertain .
Q.15: How useful is   Physical Activity??
Evidence is insufficient to conclusively show the effect of physical activity on fracture risk There are no studies that evaluated the comparative effectiveness of physical activity with that of other interventions.


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