Osteoporosis Therapy: Bone Modeling during Growth and Aging

Remodeling-based bone resorption and formation are coupled on the same surface and contribute to calcium homeostasis, while modeling-based bone formation and resorption occur on different surfaces, such as during growth, to change skeletal shape; of importance, the aging skeleton can also include bone modeling (1, 2). The primary determinant of bone modeling is elastic deformation (strain) of the skeleton engendered by habitual physical activity, and accumulating evidence suggests that bones respond to mechanical loading to maintain their resultant strain (3–5). Not only osteocytes inside bone tissue but also bone-forming osteoblasts and bone-resorpting osteoclasts on the surface are responsive to mechanical signals (6, 7), and the modeling-based actions of osteoblasts and osteoclasts are not coupled. Skeletal fragility depends on bone quality and quantity (8). The latter would be normally under the mechanical strain-related feedback control (3–5); Wolff ’s law, established more than a century ago, confirms that mechanical environment plays a key role in controlling skeletal architecture (9), and the pattern of trabecular bone in the hip (Singh index) can be used for the evaluation of osteoporosis (10). In addition, this natural homeostatic system could work against mineral-related, but not collagen-related, impairment of bone material quality (11, 12). Fragility fracture associated with osteoporosis is a common health problem during growth (13, 14) and aging (15, 16). Here, we provide a novel evidence-based insight into osteoporosis therapy from the viewpoint of bone modeling/remodeling, apart from approaches targeting bone formation/ resorption and quality/quantity.