The present study clarified the efficacy of interventions (including sunlight exposure, menatetrenone and oral bisphosphonates with vitamin D supplementation) protecting against hip fractures in elderly patients with Parkinson’s disease. Because hypovitaminosis D and K, increased bone resorption, low BMD and an increased risk of falls contribute to the risk for hip fractures in elderly patients with Parkinson’s disease[12
], these three interventions were suggested to be reasonable and effective for the management of bone health.
BMD, thickness, porosity and mean degree of mineralization in cortical bone may be important factors in determining the fracture risk at sites primarily composed of cortical bone such as the proximal femur in postmenopausal women with osteoporosis[20
]. Because most hip fractures occur due to falls, motor function may also be an important factor in the risk of hip fractures. Serum 25(OH)D is derived from both dietary intake and sunlight-induced production by the skin[22
]. The associations of hypovitaminosis D and vitamin D supplementation with the risk of falls have been confirmed in elderly persons[17
]. Sunlight exposure improves hypovitaminosis D, leading to increases in muscle strength and motor function in men and women. A decrease in bone resorption induces an increase in cortical BMD. It is documented that cortical BMD correlates positively with serum 25(OH)D concentration, particularly in the subjects with vitamin D insufficiency[24
]. Thus, improvements of muscle strength, motor function and cortical BMD might partly contribute to the prevention of hip fractures. Sunlight exposure appears to help prevent hip fractures in patients with Parkinson’s disease and hypovitaminosis D due to malnutrition and sunlight deprivation.
Vitamin K deficiency, as indicated by a high serum ucOC concentration, and low BMD may independently contribute to the risk for hip fractures in elderly persons[25
]. Menatetrenone improved hypovitaminosis K, decreased serum ucOC concentration, improved hypercalcemia and increased cortical BMD by decreasing bone resorption in women. Experimental studies showed the anti-resorptive effect of menatetrenone in various osteoporosis model animals[28
]. A recent report showed that menatetrenone maintains bone strength of the femoral neck by improving femoral neck width and maintaining the indices of compression, bending and impact strength in healthy postmenopausal women[30
]. Thus, improvements of cortical BMD, serum ucOC concentration and possibly bone geometry of the proximal femur might have partly contributed to the prevention of hip fractures. Menatetrenone appeared to be effective in preventing hip fractures in patients with Parkinson’s disease and hypovitaminosis K. However, the magnitude of hip fracture risk reduction was quite high, probably because of the bias introduced by the use of a small sample size and the low intake of natto (fermented soy bean), in terms of severe vitamin K deficiency in the recruited subjects[31
Alendronate or risedronate with vitamin D supplementation improved hypovitaminosis D, strongly decreased bone resorption, improved hypercalcemia and increased cortical BMD in men or women. Alendronate has been reported to strongly suppress bone resorption and improve femoral neck BMD, cortical thickness, cortical porosity and mean degree of mineralization of bone and thereby to prevent hip fractures in postmenopausal women with osteoporosis[20
]. The greater the suppression of bone turnover and subsequent increase in BMD are, the better the drugs are at preventing nonvertebral fractures, including hip fractures[32
]. Thus, improvements in the above parameters resulting from strong suppression of bone resorption[21
] and a decrease in the risk of falls by vitamin D supplementation[17
] may partly contribute to the prevention of hip fractures in women. Alendronate or risedronate and vitamin D supplementation appear to be quite effective for preventing hip fractures in women with Parkinson’s disease and hypovitaminosis D, as well as increased bone resorption. However, risedronate and vitamin D supplementation did not significantly reduce the incidence of hip fractures in men, probably because of less than adequate statistical power due to the lower incidence of hip fractures in men (7.4% in the placebo + vitamin D supplementation group) compared with women (11.0% in the placebo + vitamin D supplementation group).
During the trials, 4.3-9.7% of patients were dropped because of death or intercurrent illness, noncompliance or loss to follow-up. However, no severe adverse events were observed, suggesting the safety of all interventions (sunlight exposure and pharmacotherapy such as menatetrenone and oral bisphosphonates) in elderly patients with Parkinson’s disease.
Because patients with Parkinson’s disease are prone to falls, not only sunlight exposure or vitamin D supplementation, but also hip protectors and exercise aiming at the prevention of falls may help reduce the incidence of hip fractures. However, exercise therapy may be difficult for patients with very advanced Parkinson’s disease. Further studies are needed to confirm this suggestion.