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