Mitochondrial Genetics and Function as Determinants of Bone Phenotype and Aging.

While aging and sex steroid levels have traditionally been considered the most important risk factors for development of osteoporosis, mitochondrial function and genetics are being increasingly recognized as important determinants of bone health. Recent studies indicate that mitochondrial genome variants found in different human populations determine the risk of complex degenerative diseases. We propose that osteoporosis should be among such diseases. Studies have shown the deleterious effects of mitochondrial DNA mutations and mitochondrial dysfunction on bone homeostasis. Mediators of such effects include oxidative stress, mitochondrial permeability transition, and dysregulation of autophagy. Mitochondrial health plays an important role in bone homeostasis and aging, and understanding underlying mechanisms is critical in leveraging this relationship clinically for therapeutic benefit.