Bone health in Parkinson's disease: a comprehensive review of bone involvement and its pathophysiological mechanisms

Abstract

Parkinson's disease (PD) is a frequent neurodegenerative disorder that combines motor and non-motor features, including impaired balance, gait disturbances, and progressive loss of mobility. Bone involvement is well established, with low bone mass and elevated fracture risk- especially hip fractures- being common findings. Because of impaired balance, gait disturbances, cognitive dysfunction, and autonomic failure, individuals with PD experience a markedly elevated risk of falls. Osteoporosis in PD likely results from a convergence of nutritional deficiencies, vitamin D insufficiency, weight loss with sarcopenia, and progressive muscle weakness. Anti-Parkinson medications such as levodopa may also contribute through hyperhomocysteinemia. In addition, dopamine depletion and chronic inflammation may further disrupt bone remodeling. This review summarizes current evidence on bone mineral density, bone quality, falls, and fractures in PD and discusses the pathophysiological mechanisms underlying this comorbidity.

Keywords: Parkinson’s disease; bone mineral density; bone quality; falls; fractures; osteoporosis.

Figure 1

Mechanisms involved in osteoporosis in PD. Patients with PD are characterized by a low BMD resulting from multiple factors that act synergistically: nutritional factors, such as vitamin deficiencies, especially vitamin D; reduced mobility; and changes in body weight and body composition, with weight loss and decreased muscle mass leading to sarcopenia and poor muscle strength. In addition, PD medications may influence bone metabolism, as levodopa treatment induces hyperhomocysteinemia. Presumably, dopamine loss, together with an inflammatory background, contributes to impaired bone remodeling. Bone quality is also altered in PD. The motor symptoms of PD are associated with gait difficulties and postural instability, cognitive decline and dysautonomia, increasing the risk of falls. Ultimately, the combination of low BMD and an increased risk of falls leads to an increased risk of fractures, especially at the hip (PD: Parkinson’s disease; BMD: bone mineral density).