Parkinson’s disease and osteoporosis: basic and clinical implications

ABSTRACT

Introduction: Parkinson’s disease (PD) is the second most frequent neurodegenerative disease. Lewy bodies, the hallmark of this disease due to an accumulation of α-synuclein, lead to loss of dopamine-regulated motor circuits, concomitantly progressive immobilization and a broad range of nonmotor features. PD patients have more hospitalizations, endure longer recovery time from comorbidities, and exhibit higher mortality than healthy controls. Although often overlooked, secondary osteoporosis has been reported frequently and is associated with a worse prognosis.

Areas covered: In this review, we discuss the pathophysiology of PD from a systemic perspective. We searched on PubMed articles from the last 20 years in PD, both clinical features and bone health status. We discuss possible neuro/endocrine mechanisms by which PD impacts the skeleton, review available therapy for osteoporotic fractures and highlight evidence gaps in defining skeletal co-morbid events.

Expert opinion: Future research is essential to understand the local and systemic effects of dopaminergic signaling on bone remodeling and to determine how pathological α-synuclein deposition in the central nervous system might impact the skeleton. It is hoped that a systematic approach to the pathogenesis of this disease and its treatment will allow the informed use of osteoporotic drugs to prevent fractures in PD patients.

KEYWORDS:

• Parkinson’s Disease
• osteoporosis
• bone mineral density
• falls

Article Highlights

• Nonmotor symptoms in PD often occur earlier than motor dysfunction and can raise the possibility of clinically significant disease. PD patients are at high risk for fractures due to low bone mineral density (BMD), sarcopenia, and fall frequency.

• Exercise and nutritional interventions in PD patients have direct effects on bone health. However, dopaminergic-nigrostriatal circuits disruption leads to progressive alterations in neuro/endocrine signaling in PD patients that could affect directly or indirectly skeletal health by alterations in pituitary-hypothalamic axis, growth hormone, ACTH, and IGF-1 signaling.

• Osteoporotic therapies such as zoledronic acid (ZA), PTH and PTHrp analogs should be considered as potential fracture preventive therapies in PD patients.

• More research is needed to better understand the implications of α-synuclein aggregations in non-neural tissue and their impact on the skeleton.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The paper was funded by NIGMS P20121301.