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\nMurray J.Favus,M.D: Bisphosphonates for Osteoporosis. N Eng J MED 363;2027-35, 2010.\u2028\u2028\u2028<\/p>\n
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\u3010The clinical problem\u3011
\nEstrogen deficiency after menopause is the most common cause of osteoporosis, but secondary causes must be ruled out before treatment is undertaken.
\nCommon Secondary Causes of Osteoporosis are Vitamin D deficiency, Primary hyperparathyroidism, Celiac disease, Idiopathic hypercalciuria, Hyperthyroidism, Myeloma.
\nOsteoporotic hip fractures are associated with the highest morbidity and mortality. Up to 50% of patients with such fractures have permanently impaired mobility, and 25% lose the skills necessary to live independently. The rate of death from any cause is increased by a factor of 5 to 8 during the first 3 months after a hip fracture.
\n\u3010Pathophysiology\u3011
\nEstrogen deficiency due to either spontaneous or surgical menopause activates osteoclast and accelerate bone resorption. Bisphosphonates disrupt the attachment of osteoclasts to the bone surface, and stop bone resorption.
\n\u3010Clinical Evidence\u3011
\nAlendronate and risedronate and zoledronic acid are effective to prevent hip fracture and vertebral fracture.
\n\u00a0Etidronate is effecitive to prevent vertebral fracture, but there is no study to show efficacy for the
\ntreatment of hip fracture.
\n\u00a0Randomized, placebo-controlled trial of pamidronate has not been performed with sufficient power to assess the efficacy of the drug for the treatment of hip fracture in women with postmenopausal osteoporosis.
\n\u3010Clinical use\u3011
\nAll postmenopausal women with measurements of bone mineral density at either the spine or the hip that meet World Health Organization (WHO) criteria for osteoporosis (T score of less than \u22122.5) should receive long-term therapy with an agent that has been proven to prevent fractures.
\nThis author often uses the WHO Fracture Risk Assessment Tool (http:\/\/www.sheffield.ac.uk\/FRAX\/tool.jsp?lang=jp) to assist in making treatment decisions. FRAX is a calculator algorithm that incorporates risk factors with measurements of bone mineral density, generating a quantitative estimate of the 10-year probability of a major osteoporotic
\nfracture (hip, vertebral, humerus, or fore-arm) or of a hip fracture alone in patients who have not yet begun therapy. In general, the author initiates pharmacologic treatment in patients who have a 10-year probability of a hip fracture that exceeds 3% or a 10-year probability of a major osteoporotic fracture that exceeds 20%.
\nRaloxifene decreases the risk of vertebral fractures, but it may not reduce the risk of nonvertebral fractures.
\nCalcitonin has limited efficacy in reducing the risk of vertebral fractures and lacks efficacy in preventing hip fracture.
\nAfter initiating bisphosphonate therapy, this author typically reevaluate the patient in 1 month to assess tolerance and thereafter at 3 months, 6 months,and 1 year. At 3 months and 6 months, he obtain measurements of bone-turnover markers, such as osteocalcin or serum C-terminal telopeptide of type 1 collagen (CTX). At 1 year, and every 2 years thereafter, he repeat the assessment of bone mineral density with the use of DXA.
\n\u3010Adverse effects\u3011
\n\u00a0Erosive esophagitis, ulceration, and bleeding, heartburn, chest pain, hoarseness, and vocal-cord irritation, transient renal toxic effects, osteonecrosis of the jaw, etc.
\n\u3010Areas of uncertainty\u3011
\n\u00a0 The optimal duration of bisphosphonate therapy remains uncertain. Recent retrospective studies and case reports suggest that long-term bisphosphonate therapy may result in the suppression of bone turnover and confer a predisposition to increased bone fragility, with an increased risk for atypical femur fractures. After 5 years of treatment, this author would decide whether a drug holiday might be appropriate for this patient, taking into consideration the fact that she is at high risk for recurrent fracture.
\n\u2028\u2028\u3010\u8003\u5bdf\u3068\u30c7\u30a3\u30b9\u30ab\u30c3\u30b7\u30e7\u30f3\u3011
\n\u9aa8\u7c97\u9b06\u75c7\u306b\u5bfe\u3059\u308b\u30d3\u30b9\u30d5\u30a9\u30b9\u30d5\u30a9\u30cd\u30fc\u30c8\u88fd\u5264\u306b\u95a2\u3059\u308b\u6700\u65b0\u306e\u30ec\u30d3\u30e5\u30fc\u3092\u8aad\u3093\u3060\u3002\u2028FRAX\u3068\u3044\u3046\u9aa8\u6298\u306e\u30ea\u30b9\u30af\u8a55\u4fa1\u6cd5\u3092\u5b66\u3093\u3060\u3002\u2028Areas of uncertainty\u306e\u9805\u3067\u306f\u30d3\u30b9\u30d5\u30a9\u30b9\u30d5\u30a9\u30cd\u30fc\u30c8\u88fd\u5264\u306e\u9577\u671f\u7684\u306a\u4f7f\u7528\u304c\u30b3\u30c4\u306e\u8106\u5f31\u6027\u3092\u5f15\u304d\u8d77\u3053\u3059\u53ef\u80fd\u6027\u3092\u793a\u5506\u3059\u308b\u30ec\u30c8\u30ed\u30b9\u30da\u30af\u30c6\u30a3\u30d6\u306a\u7814\u7a76\u3068\u3001\u3053\u306e\u85ac\u5264\u306b\u3088\u308b\u6cbb\u7642\u306e\u671f\u9593\u306b\u3064\u3044\u3066\u8a00\u53ca\u3057\u3066\u3044\u308b\u3002\u2028\u4eca\u5f8c\u306e\u30a8\u30d3\u30c7\u30f3\u30b9\u306e\u51fa\u73fe\u306b\u6ce8\u610f\u3057\u3064\u3064\u3001\u5b9f\u969b\u306e\u81e8\u5e8a\u306b\u304a\u3044\u3066\u3082\u6cbb\u7642\u7d99\u7d9a\u671f\u9593\u3092\u898b\u76f4\u3059\u5fc5\u8981\u304c\u3042\u308b\u3060\u308d\u3046\u3002\u2028<\/p>\n
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