Giant Osteoclast Formation and Long-Term Oral Bisphosphonate Therapy

• Published in: The New England journal of medicine Vol. 360; no. 1; pp. 53 - 62
• Main Authors: Weinstein, Robert S, Roberson, Paula K, Manolagas, Stavros C
• Format: Journal Article
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 01.01.2009
• Subjects: Acid Phosphatase - analysis; Adult; Alendronate - pharmacology; Alendronate - therapeutic use; Apoptosis; Apoptosis - drug effects; Biological and medical sciences; Biopsy; Bone and Bones - cytology; Bone and Bones - pathology; Bone density; Bone Density Conservation Agents - pharmacology; Bone Density Conservation Agents - therapeutic use; Bone Remodeling - drug effects; Dose-Response Relationship, Drug; Double-Blind Method; Drug dosages; Female; General aspects; Humans; Isoenzymes - analysis; Linear Models; Medical sciences; Middle Aged; Nitrogen; Older people; Osteoclasts - chemistry; Osteoclasts - cytology; Osteoclasts - drug effects; Osteoclasts - pathology; Osteoporosis; Postmenopause; Tartrate-Resistant Acid Phosphatase; Medicine; Antiosteoporotic; Antiosteoclastic agent; Oral administration; Osteoclast; Bisphosphonates; Formation; Long term
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa0802633

This study examined bone-biopsy specimens obtained after a 3-year, double-blind, randomized, placebo-controlled, dose-ranging trial of oral alendronate to prevent bone resorption in healthy postmenopausal women. Long-term alendronate treatment was associated with an increase in the number of osteoclasts, which include distinctive giant, hypernucleated, detached osteoclasts that undergo protracted apoptosis. The finding of such cells, despite decreased resorption after long-term therapy with oral nitrogen-containing bisphosphonate, may have clinical implications. In healthy postmenopausal women, long-term alendronate treatment was associated with an increase in the number of osteoclasts, which include distinctive giant, hypernucleated, detached osteoclasts that undergo protracted apoptosis. Bisphosphonates are used worldwide to prevent fractures in patients with osteoporosis. 1 – 6 Treatment with these drugs decreases the rate of bone resorption and levels of biochemical markers of bone turnover and causes progressive increases in bone mineral density. The clinical efficacy of nitrogen-containing bisphosphonates is widely believed to result from their potent ability to decrease the number of osteoclasts by promoting their apoptosis. 7 – 9 Once osteoclasts become apoptotic, they are usually quickly ingested by bone marrow phagocytes. 10 However, enumeration of osteoclasts in specimens of cancellous bone (bone composed of multiple trabecular structures) obtained from patients treated with nitrogen-containing bisphosphonates shows . . .