Murray J.Favus,M.D: Bisphosphonates for Osteoporosis. N Eng J MED 363;2027-35, 2010.
【The clinical problem】
Estrogen deficiency after menopause is the most common cause of osteoporosis, but secondary causes must be ruled out before treatment is undertaken.
Common Secondary Causes of Osteoporosis are Vitamin D deficiency, Primary hyperparathyroidism, Celiac disease, Idiopathic hypercalciuria, Hyperthyroidism, Myeloma.
Osteoporotic 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.
Estrogen 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.
Alendronate and risedronate and zoledronic acid are effective to prevent hip fracture and vertebral fracture.
Etidronate is effecitive to prevent vertebral fracture, but there is no study to show efficacy for the
treatment of hip fracture.
Randomized, 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.
All 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 −2.5) should receive long-term therapy with an agent that has been proven to prevent fractures.
This 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
fracture (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%.
Raloxifene decreases the risk of vertebral fractures, but it may not reduce the risk of nonvertebral fractures.
Calcitonin has limited efficacy in reducing the risk of vertebral fractures and lacks efficacy in preventing hip fracture.
After 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.
Erosive esophagitis, ulceration, and bleeding, heartburn, chest pain, hoarseness, and vocal-cord irritation, transient renal toxic effects, osteonecrosis of the jaw, etc.
【Areas of uncertainty】
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.
骨粗鬆症に対するビスフォスフォネート製剤に関する最新のレビューを読んだ。 FRAXという骨折のリスク評価法を学んだ。 Areas of uncertaintyの項ではビスフォスフォネート製剤の長期的な使用がコツの脆弱性を引き起こす可能性を示唆するレトロスペクティブな研究と、この薬剤による治療の期間について言及している。 今後のエビデンスの出現に注意しつつ、実際の臨床においても治療継続期間を見直す必要があるだろう。