Recovery of Trabecular and Cortical Bone Turnover After Discontinuation of Risedronate and Alendronate Therapy in Ovariectomized Rats

• Published in: Journal of bone and mineral research Vol. 23; no. 10; pp. 1689 - 1697
• Main Authors: Fuchs, Robyn K, Phipps, Roger J, Burr, David B
• Format: Journal Article
• Language: English
• Published: Washington, DC John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR) 01.10.2008; American Society for Bone and Mineral Research; Amer Soc Bone & Mineral Res
• Subjects: alendronate; Alendronate - administration & dosage; Animals; Biological and medical sciences; bisphosphonates; Body Weight; Bone Density; Bone Density Conservation Agents - administration & dosage; Bone Remodeling; Etidronic Acid - administration & dosage; Etidronic Acid - analogs & derivatives; Female; Fundamental and applied biological sciences. Psychology; Original; Ovariectomy; Rats; Rats, Sprague-Dawley; risedronate; Risedronate Sodium; Skeleton and joints; treatment withdrawal; Vertebrates: osteoarticular system, musculoskeletal system; Ovariectomy; Rat; Rodentia; Antiresorptive agent; Diphosphonic acid derivatives; Bisphosphonates; risedronate; Osteoarticular system; Alendronic acid; Vertebrata; Mammalia; Risedronic acid; Treatment withdrawal; Turnover; alendronate; Cortical bone
• ISSN: 0884-0431; 1523-4681; 1523-4681
• DOI: 10.1359/jbmr.080501

Alendronate (ALN) and risedronate (RIS) are bisphosphonates effective in reducing bone loss and fractures associated with postmenopausal osteoporosis. However, it is uncertain how long it takes bone turnover to be re‐established after treatment withdrawal, and whether this differs between the two drugs. The objective of this study was to determine the time required to re‐establish normal bone turnover after the discontinuation of ALN and RIS treatment in an animal model of estrogen‐deficiency osteoporosis. Two hundred ten, 6‐mo‐old female Sprague‐Dawley rats were ovariectomized and 6 wk later were randomized into baseline controls (n = 10) and four treatment groups (n = 50/group): vehicle‐treated controls (CON; 0.3 ml sterile water), ALN (2.4 μg/kg), low‐dose RIS (RIS low; 1.2 μg/kg), and high‐dose RIS (RIS high; 2.4 μg/kg). Treatments were administered 3 times/wk by subcutaneous injection. Baseline controls were killed at the initiation of treatment. Other groups were treated for 8 wk, and subgroups (n = 10/ treatment group) were killed 0, 4, 8, 12, and 16 wk after treatment was withdrawn. Static and dynamic histological analyses were performed for cortical (tibial diaphysis) and trabecular (proximal tibia and L4 vertebrae) bone. DXA and mechanical testing was performed on the L5 vertebra. After 8 wk of treatment, trabecular bone turnover rates were significantly suppressed in all drug‐treated animals. Trabecular bone formation rate (BFR/BS) remained significantly lower than vehicle in bisphosphonate‐treated animals through 12 wk. Sixteen weeks after treatment withdrawal, trabecular BFR/BS in the proximal tibia was re‐established in animals treated with RIS but not in animals treated with ALN compared with controls. BMD of the fifth lumbar vertebra remained significantly higher than controls 16 wk after treatment withdrawal in ALN‐treated animals but not in RIS‐treated animals. Despite reductions in BMD and increases in bone turnover, ultimate force of the fifth lumbar vertebra remained significantly higher in all drug‐treated animals through 16 wk after withdrawal.