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Osteoporosis Pathogenesis and risk factors

Osteoporosis: Pathogenesis and risk factors Primary Osteoporosis Bone loss that occurs during normal human aging (e.g. Age > 30, post-menopausal women, and genetics). Secondary Osteoporosis Smoking, alcohol, ↓ exercise, chronic malnutrition, hyperthyroidism, hyperparathyroidism, corticosteroid use, ↓ vitamin D, bone malignancies, chronic kidney or liver disease, and malabsorption. Reduced peak bone mass achieved during skeletal growth and/or an imbalance in the factors favoring bone resorption compared to bone formation in adult bone ↓ Serum vitamin D from malabsorption, poor nutrition, or chronic liver/ kidney disease ↓ Serum activated vitamin D (precursor for Ca2+ transporters in the gut) ↓ Ca2+ absorption from gut ↓ Ca2+ available for mineralization of bone matrix Age related bone degeneration and ↓ exercise ↑ Reactive oxygen species (ROS) systemically due to aging ↑ Oxidative stress on bone ↑ Osteocyte death in cortical bones ↓ Bone Formation ↓ Estrogen in post-menopausal women Hyperparathyroidism/ bone malignanciesà ↑ parathyroid hormone (PTH) or parathyroid hormone-related (PTHR) protein released ↑ PTH and PTHR peptide receptor signaling in osteocytes results in ↓ osteoprotegerin (OPG) expression ↓ OPG secretion Hyperthyroidism à↑ T3 and T4 ↑ Thyroid receptor- alpha-1 activation (located in bones) ↑ Osteoclasts (cells that break down bone) ↑ Bone Resorption Corticosteroid use ↑ Corticosteroid binding to glucocorticoid receptors on bone suppresses OPG expression in bone Smoking Multiple mechanisms (e.g. ↓ blood supply to bone, ↑ free radicals, direct effects on RANKL/RANK/ OPG bone remodeling axis leading to alterations in osteogenesis ↑ Bone Resorption and ↓ Bone Formation Abbreviations: • T3 - Triiodothronine • T4 - Thyroxine ↓ Stimulation of OPG transcription in osteoblasts Authors: Ben Wajda, Arsalan Ahmad, Lance Bartel Reviewers: Alyssa Federico, Mehul Gupta, Tara Shannon, Reza Ojaghi, Usama Malik, Carol Hutchinson*, David Hogan* * MD at time of publication ↓ Inhibition of receptor activator of nuclear factor kappa-B ligand (RANKL) (receptor that stimulates osteoclast growth) Osteoporosis: Imbalance of bone formation and resorption leading to decreased bone mineral density and bone mass, or quality changes that lead to a decrease in bone strength and an increase risk of fractures Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published May 20, 2022 on www.thecalgaryguide.com