Alendronate does not prevent long bone fragility in an inactive rat model.

Area of Science:

• Gerontology
• Orthopedics
• Pharmacology

Background:

• Osteoporosis pathogenesis in elderly women involves estrogen deficiency and inactivity.
• Rodent models are needed to study bisphosphonate efficacy against these factors separately.
• Alendronate (ALN) is a common bisphosphonate used to treat osteoporosis.

Purpose of the Study:

• To compare the efficacy of alendronate (ALN) on aged female rats that were sedentary, estrogen-deficient, or both.
• To investigate the effects of inactivity and estrogen deficiency on bone health.
• To evaluate ALN's effectiveness in mitigating bone deterioration under different conditions.

Main Methods:

• Aged female rats underwent ovariectomy or sham surgery, followed by an 8-week experimental period.
• Rats were either sedentary (sitting position) or active (walking in cages), with or without ALN administration.
• Bone parameters were assessed using mechanical testing, CT scans, microspectroscopy, and histomorphometry.

Main Results:

• ALN was ineffective against reduced breaking stress caused by inactivity, despite increased bone mineral density in sedentary ALN-treated groups.
• Inactivity led to decreased bone toughness, altered geometry (larger marrow space), and signs of aged bone (increased mineral-to-matrix and carbonate-to-phosphate ratios).
• Sitting caused deficits in cortical bone quality and geometry, resulting in fragility, even with ALN treatment.

Conclusions:

• Alendronate (ALN) does not prevent bone fragility induced by inactivity in aged female rats.
• Inactivity significantly impairs bone quality and geometry, leading to fragility.
• Bisphosphonate therapy may be most suitable for osteoporotic individuals who are not limited by daily activity.