Emerging Treatment Approaches for Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease, manifesting as a characteristic movement disorder with a number of additional non-motor features. The pathological hallmark of PD is the presence of intra-neuronal aggregates of α-synuclein (Lewy bodies). The movement disorder of PD occurs largely due to loss of dopaminergic neurons of the substantia nigra, resulting in striatal dopamine depletion. There are currently no proven disease modifying treatments for PD, with management options consisting mainly of dopaminergic drugs, and in a limited number of patients, deep brain stimulation. Long-term use of established dopaminergic therapies for PD results in significant adverse effects, and there is therefore a requirement to develop better means of restoring striatal dopamine, as well as treatments that are able to slow progression of the disease. A number of exciting treatments have yielded promising results in pre-clinical and early clinical trials, and it now seems likely that the landscape for the management of PD will change dramatically in the short to medium term future. Here, we discuss the promising regenerative cell-based and gene therapies, designed to treat the dopaminergic aspects of PD whilst limiting adverse effects, as well as novel approaches to reducing α-synuclein pathology.

A service development study of the assessment and management of fracture risk in Parkinson's disease.

Parkinson's disease (PD) is associated with an increased risk of fragility fracture. FRAX and Qfracture are risk calculators that estimate the 10-year risk of hip and major fractures and guide definitive investigation for osteoporosis using dual X-ray absorptiometry (DEXA) imaging. It is unclear which PD patients should be considered for fracture risk assessment and whether FRAX or Qfracture should be used. Seventy-seven patients with PD were recruited in the movement disorders clinic. Data were collected on PD-related characteristics and fracture risk scores were calculated. Patients with previous osteoporotic fractures had a higher incidence of falls (p = 0.0026) and use of bilateral walking aids (p = 0.0187) in addition to longer disease duration (p = 0.0037). Selecting patients with falls in combination with either disease duration >5 years, bilateral walking aids, or previous osteoporotic fracture distinguished patients with and without previous osteoporotic fracture with specificity 67.7 % (95 % CI 55.0-78.8) and sensitivity 100.0 % (95 % CI 73.5-100.0). Qfracture calculated significantly higher fracture risk scores than FRAX for hip (p < 0.0001) and major (p = 0.0008) fracture in PD patients. Receiver operating characteristic curves demonstrated that FRAX outperformed Qfracture with an area under the curve of 0.84 (95 % CI 0.70-0.97, p = 0.0004) for FRAX and 0.68 (95 % CI 52-86, p = 0.0476) for Qfracture major fracture risk calculators. We suggest that falls in combination with either a disease duration longer than 5 years or bilateral walking aids or previous osteoporotic fracture should be used as red flags in PD patients to prompt clinicians to perform a FRAX fracture risk assessment in the neurology clinic.

Bone health in Parkinson's disease: a systematic review and meta-analysis.

OBJECTIVE: Parkinson's disease (PD) and osteoporosis are chronic diseases associated with increasing age. Single studies have reported associations between them and the major consequence, namely, increased risk of fractures. The aim of this systematic review and meta-analysis was to evaluate the relationship of PD with osteoporosis, bone mineral density (BMD) and fracture risk. METHODS: A literature search was undertaken on 4 September 2012 using multiple indexing databases and relevant search terms. Articles were screened for suitability and data extracted where studies met inclusion criteria and were of sufficient quality. Data were combined using standard meta-analysis methods. RESULTS: 23 studies were used in the final analysis. PD patients were at higher risk of osteoporosis (OR 2.61; 95% CI 1.69 to 4.03) compared with healthy controls. Male patients had a lower risk for osteoporosis and osteopenia than female patients (OR 0.45; 95% CI 0.29 to 0.68). PD patients had lower hip, lumbar spine and femoral neck BMD levels compared with healthy controls; mean difference, -0.08, 95% CI -0.13 to -0.02 for femoral neck; -0.09, 95% CI -0.15 to -0.03 for lumbar spine; and -0.05, 95% CI -0.07 to -0.03 for total hip. PD patients were also at increased risk of fractures (OR 2.28; 95% CI 1.83 to 2.83). CONCLUSIONS: This systematic review and meta-analysis demonstrate that PD patients are at higher risk for both osteoporosis and osteopenia compared with healthy controls, and that female patients are at greater risk than male patients. Patients with PD also have lower BMD and are at increased risk of fractures.