Recent studies have shown that genetic effects on bone mineral density (BMD) and bone turnover are related to allelic variation in the vitamin D receptor (VDR) gene. We examined allelic influences of the VDR gene on bone turnover and density in 202 normal healthy premenopausal Japanese women (age 30.1 +/- 1.2, mean +/- SEM). The VDR effect on BMD and turnover is similar to that observed in Caucasian women; however, there are major differences in allele frequency. The B allele by BsmI restriction fragment length polymorphisms (RFLPs), associated with low BMD and high bone turnover, is found in only 12% of Japanese women (1.4% homozygote BB), compared with 41% of Caucasians (16.7% homozygote BB). In comparing the two most frequent genotypes, Bb heterozygotes (21.5%) and bb homozygotes (77.1%), BMD is 5.3% lower in Bb heterozygotes, and levels of bone formation markers including osteocalcin and bone-specific alkaline phosphatase are 20-32% higher with lower serum calcium (2.30 +/- 0.02 vs 2.35 +/- 0.01 mmol/l) and higher 1,25-dihydroxyvitamin D (95 +/- 4.8 vs. 76 +/- 3.8 pmol/l). Further discrimination of the genotype was achieved using two additional RFLPs (ApaI, A and TaqI, T); the lumbar spine BMD of the common genotype BbAATt was 9.3% (0.94 SD) lower than in the bbaaTT genotype in premenopausal Japanese women. These data confirm that VDR RFLPs affect bone mineral metabolism regardless of racial differences. Moreover, the VDR genotypes based on haplotype analysis should yield useful insights into the potential prevention of osteoporosis.

SummaryThis multi-center, prospective, open-label, observational study evaluated the effects of once-monthly minodronate (50 mg) on treatment persistence, bone turnover markers, bone mineral density, low back pain, and upper gastrointestinal symptoms in outpatients with osteoporosis previously treated with daily or weekly bisphosphonate products.IntroductionThe purposes of this study were to investigate the effects of once-monthly oral minodronate (MIN 50 mg) on bone turnover markers and bone mineral density, low back pain, and upper gastrointestinal symptoms, as well as preference for and treatment persistence of MIN 50 mg among Japanese osteoporosis patients currently treated with daily or weekly bisphosphonates.MethodsStudy patients were allocated based on their preference to either the Switch group (patients willing to switch over to MIN 50 mg) or the Continue group (patients wanting to continue their current therapies). Patients’ treatment persistence and satisfaction levels with the therapies were assessed using a self-administered questionnaire. The study endpoints were serum TRACP-5b, serum P1NP, bone mineral density, upper gastrointestinal symptoms, and low back pain.ResultsIn total, 264 and 133 patients were allocated into the Switch and Continue groups, respectively. Approximately, 65 % of patients were willing to switch to MIN 50 mg, with the predominant reason being “less frequent dosing more convenient.” Treatment persistence was significantly higher in the Switch group (MIN 50 mg) than the Continue group. Almost all patients with abnormal bone metabolism markers demonstrated normalization after switchover. MIN 50 mg alleviated low back pain and upper gastrointestinal symptoms induced by prior bisphosphonate use.ConclusionsMIN 50 mg alleviates low back pain, reduces bone turnover markers and increases bone density, and induces fewer upper gastrointestinal symptoms after switchover from prior bisphosphonate products, and therefore, it may provide patients with a more convenient treatment option and enhance long-term treatment persistence.

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Treatment of osteoporosis with once-yearly zoledronic acid was approved in September 2016 in Japan. Like other bisphosphonates, zoledronic acid causes acute-phase responses (APRs), which are more severe in Asian populations than in multinational populations. The aim of this multicenter, randomized, open label, parallel group study is to investigate the incidence of APRs in Japanese patients with primary osteoporosis in real clinical settings, and to test the hypotheses that APRs are suppressed by administering one of the most commonly used nonsteroidal anti-inflammatory drugs in Japan, loxoprofen, immediately after the treatment with zoledronic acid, and the incidence of APRs in patients with prior history of treatment with bisphosphonate is lower than that in naïve patients. A total of 400 patients aged 60 or older were randomly allocated to a zoledronic acid plus loxoprofen group or zoledronic acid group on a 1:1 basis. After the treatment, patients were observed for 7 days, during which patients will record APRs for the first 3 days, and body temperature and drugs taken for 7 days. Primary endpoints are incidence of APRs and increase in body temperature, and secondary endpoints are relationship between prior treatment for osteoporosis in the past 3 years versus incidence of APRs, and that versus a change in body temperature. Results supporting the hypotheses will indicate that APRs are manageable with loxoprofen, which patients likely already have, and the APRs will develop less frequently and be less severe in the following years, despite the high risk of APRs in Japanese patients.