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Understanding Osteoporosis: Aging, Bone Density, and Current Research Insights

Osteoporosis is a clinically significant condition characterized by bone fractures due to decreased bone density, particularly affecting the elderly. Aging leads to reduced trabecular thickness, cortical bone density, and increased porosity, contributing to health risks when fractures occur. As the U.S. population ages, addressing bone loss becomes increasingly critical. Research indicates a complex interaction of factors, including changes in osteoblast and osteoclast activity, as well as immune response in aging models. Ongoing studies explore these mechanisms to improve prevention and treatment strategies.

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Understanding Osteoporosis: Aging, Bone Density, and Current Research Insights

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  1. Lab Meeting January 24, 2012

  2. Osteoporosis • Clinical osteoporosis, defined as bone fracture related to decreased bone density, is on of the most physically debilitating conditions associated with aging. • In older people, the temporary immobilization associated with a facture often precipitates a period of reduced physical activity or permanent physical disability. • As the US population becomes increasingly older, understanding and minimizing aging-related bone lose is increasingly becoming a national priority.

  3. Indicates of Aging Human Bone • Decreased trabecular thickness • Decreased cortical bone • Increased bone porosity • Decreased bone formation rate • Decreased number of osteoblasts • Decreased number of osteoclasts • Increased number of adipocytes Jee WSS and Yao W J Musculoskel Neuron Interact 2001

  4. Current Models of Osteoporosis • Ovariectomy (Wronksi, et al. Calcif Tissue Int 1988; Wronksi, et al. Calcif Tissue Int 1989; Wronksi, et al. Calcif Tissue Int 1992; Kalu, DN Bone Miner 1991; Seedor, et al. J Bone Miner Res 1991; Black, et al. Calcif Tissue Int 1989) • Immobilization (Jee, et al. J Histotech 1997; Jee, WSS and Ma, YF Morphologie 1999) • Treatment with particular factors (ie glucocorticoid) (Weinstein, et al. J Clin Invest 1998; Mangolagas, et al. J Bone Miner Res 1999)

  5. Wrn-/-Terc-/- Aging Model • Dyskeratosis Congenita (DC) (Terc) • Werner syndrome (WS) (Wrn) • Accelerated aging diseases in humans (premature osteoporosis) • Terc-/- mice lack detectable telomerase activity and are viable for the six generations analyzed. Early generations of Terc-/- mice show little change in telomere length and no premature aging phenotypes. But in subsequent generations (5 to 6), the telomeres shrink and mice show a number of premature aging phenotypes, including gray hair, increased incidence of spontaneous malignancies, and decreased life-span. (Sci. Aging Knowl. Environ., 2003) • Wrn-/-Terc-/- mice have a low bone mass phenotype shown by DXA on 14.7 month old mice, and that age-related osteoporosis is the result of impaired osteoblast differentiation. (Pignolo, et al Aging Cell 2008)

  6. Trabecular Bone Parameters WT Wrn-/- Terc-/- Wrn-/-/Terc-/-

  7. Cortical Bone Parameters WT Wrn-/- Terc-/- Wrn-/-/Terc-/-

  8. WT Wrn-/-/Terc-/- 10x magnification

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