TAGAWA, Japan -- Low-dose bisphosphonate therapy may help reduce the high rate of hip fractures among men with Parkinson's disease, Japanese researchers found.
TAGAWA, Japan, March 19 -- Low-dose bisphosphonate therapy may help reduce the high rate of hip fractures among men with Parkinson's disease, Japanese researchers found.
Men with Parkinson's given risedronate (Actonel) plus vitamin D2 were one-third as likely to suffer hip fracture as those given placebo and vitamin D2, said Yoshihiro Sato, M.D., of Mitate Hospital here, and colleagues.
Risedronate also increased bone mineral density by 2.2% over the two years of the study whereas it fell 2.9% with placebo, they reported in the March 20 issue of Neurology.
In the study, risedronate was given at the 2.5 mg/day dose approved in Japan. In the United States, 5 mg is the dose approved by the FDA for prevention and treatment of postmenopausal osteoporosis in women and glucocorticoid-induced osteoporosis in men and women.
The prospective study included 242 men (mean age 72.2) with Parkinson's disease but who were otherwise healthy without renal, hepatic, cardiac, or thyroid dysfunction.
The median Parkinson's severity was stage 3.0 on the Hoehn and Yahr scale. About 80% of patients in both groups got less than 15 minutes of sun exposure a week because of reduced mobility, which put them at risk for low levels of vitamin D that may contribute to osteoporosis.
None had been taking potentially confounding medications, had total disability, or had a previous history of nonvertebral fractures.
Participants were randomized to a daily 2.5-mg risedronate tablet before breakfast and 1,000 IU vitamin D2 (ergocalciferol) after breakfast or a placebo and the same vitamin D2 dose. They were periodically checked for hip fracture. Bone mineral density of the second metacarpal was measured with an x-ray densitometer at baseline and one and two years later.
After two years of treatment, there were nine hip fractures in the placebo group and three in the risedronate group.
The relative risk of hip fracture was therefore 0.33 with risedronate versus placebo (95% confidence interval 0.09 to 1.20). This difference was despite a similar number of falls in the two groups (1.5 1.6 and 1.5 1.5 per person, respectively).
Both groups started with a mean bone mineral density T-score of 2.25 indicating osteoporosis. Over the two year period, bone mineral density increased in the risedronate group but decreased in the placebo group (+2.2% 0.2 versus -2.9% 0.2, P<0.001).
A marker of bone resorption, urinary deoxypyridinoline, also showed more improvement in the risedronate group than in the placebo group (46.7% versus 33.0% decrease). The researchers said this is consistent with inhibition of immobilization-induced bone resorption.
No serious adverse events were reported. However, three risedronate group patients had esophagitis. Four patients in the risedronate group and three in the placebo group experienced abdominal pain. These cases "eventually healed with appropriate therapy without discontinuation of treatment," Dr. Sato and colleagues wrote.
His research group previously showed that another bisphosphonate, alendronate (Fosamax), prevented hip fractures in elderly women with Parkinson's (relative risk 0.29 versus placebo).
Thus, they said their studies supported a "noteworthy" effect for both risedronate and alendronate.
"The results demonstrated that the active treatment does have a clinically significant influence on progressive demineralization of bone in [Parkinson's disease]," they wrote. "It is also effective, as demonstrated in the present study, despite other deleterious factors such as 25-OHD [hydroxyvitamin D] insufficiency and disuse."
The investigators cautioned, though, that vitamin D therapy should not be combined with calcium supplementation "since such therapy may further increase hypercalcemia."