Bone turnover and agerelated bone loss

Bone is continuously broken down and replaced throughout life, thereby mobilizing calcium for systemic needs and preventing the accumulation of old fatigue-fractured material. Typically, 4% of cortical bone and 25% of trabecular bone are replaced each year.

Turnover begins with the recruitment of osteo-clast precursors. These mature, fuse into multinucle-ate osteoclasts, and resorb a depression 60 mg deep in the bone surface over a period of about 10 days. Osteoblasts derived from undifferentiated cells located in the vicinity of the resorption site then replace the resorbed material. The entire process lasts approximately 4 months.

After the fourth decade of life, bone reformation fails to replace completely the resorbed bone, so that bone turnover produces a net bone loss. This so-called 'age-related bone loss' (0.3% and 1% of peak bone mass per year in males and females, respectively) occurs regardless of sex, physical activity, nutrition, or socioeconomic status. Its rate depends upon the frequency of remodeling cycles and the imbalance between the amount of bone resorbed and replaced at each remodeling event.

Age-related bone loss therefore occurs more rapidly in trabecular bone (which turns over more rapidly) and is increased by factors that promote bone turnover (transient calcium deficiency). Risk factors or disease states associated with either low peak bone mass or increased rates of loss include small body size, nulli-parity, inactivity, early natural menopause, anorexia, thyrotoxicosis, and Cushing's syndrome.

Ultimately, the combination of reduced bone mass and disrupted trabecular architecture (as individual bony struts are severed or removed from the lattice) leads to reduced bone strength and increased fracture risk.

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