The present study found that daily treatment with Maxmarvil for 12 months resulted in an increase in lumbar BMD. Considering the LSC for each hospital, we found that 167 subjects (45.1%) showed BMD improvement. Factors associated with BMD improvement were good compliance and continuation of treatment.
In the current study, the average improvement in lumbar BMD was 3.4% ± 6.4%. Another study conducted in Korea also using Maxmarvil reported a BMD increase of 2.42% ± 0.5% after 24 weeks of treatment.16)
It is interesting that that amount of improvement was somewhat similar given that the treatment period was about half the duration of that in the present study. In a randomized open study including 226 postmenopausal women with osteoporosis, 10 mg alendronate plus 0.5 µg alfacalcidol for 12 months was found to increase BMD by 4.3%.
The generally recommended dosage of alendronate is 10 mg daily or 70 mg weekly. However, previous studies conducted in Japan showed that 5 mg/d of aldendronate for 3 years was also effective in increasing BMD and reduced the risk of vertebral fractures.8)
In addition, another study reported that 2.5 mg/d of alendronate had a positive effect on BMD, and that the effect was not significantly different from a 10 mg/d dosage.17)
Compared with Caucasians, Asians have smaller body size and a lower dietary intake of calcium, therefore the recommended drug dosage established for Caucasians may not be appropriate for Asians.17)
Vitamin D deficiency is now a worldwide problem even in developed countries. In Korea, the prevalence of 25(OH) D levels less than 50 nmol/L during the wintertime is reported to be 90.1%.18)
Furthermore, calcium intake for most Koreans is below the RDA. In the present study, no patients had a daily calcium intake >1,500 mg, which is the RDA for postmenopausal women. The superiority of calcitriol compared to native vitamin D in preventing bone loss and fractures has been established. In addition, combined treatment with alendronate and vitamin D analogs seems to be more effective, as compared to the respective monotherapies.19)
In the present study, multivariate analysis, which adjusted for age and other factors, found that continuation of treatment and good compliance were associated with BMD improvement. Drug compliance and adherence are important factors in successful treatment. In a previous study of postmarketing surveillance for the efficacy and safety of residronate, good compliance was associated with BMD improvement.20)
And studies assessing the consequences of poor compliance and persistence in patients who did not follow their dosing regimens demonstrated lower BMD gains and increased risk of fracture.21
Dosing frequency is one of the factors contributing to poor adherence, and despite the daily regimen of Maxmarvil, the compliance and persistence in our study was high (65% and 87.7%, respectively). This may reflect the use of a combined drug, as against having to take bisphosphonate and calcitriol separately.
The present study used the simple SQFFQ to obtain calcium intake information. Using 500 mg/d of calcium as a referent, patients with an intake of ≥500 mg/d had an odds ratio for BMD improvement of 0.68 (95% confidence interval, 0.41 to 1.13). No association was observed between calcium intake and BMD improvement, either before or after adjustment. BMD improvement from calcium intake was expected to be relatively small because the efficacy of Maxmarvil was great. However, recall bias cannot be completely excluded because the measurement method used was a self-reporting questionnaire.
Drug safety is a critical issue. The overall adverse event rate in this study was 5.6%. Abdominal pain and dyspepsia were the most common adverse events, and accounted for more than half of the total events. The types of adverse events in this study did not differ from those reported in other bisphosphonate studies.23
The proportion of patients who experienced adverse events that led to discontinuation was 2.8% (16 patients). Therefore, Maxmarvil was found to be well tolerated with no serious adverse events and showed a low dropout rate during the study period.
The significance of this study is that it was a multicenter study conducted at 12 medical centers targeting people from various regions, which differentiates it from other studies. In addition, unlike other studies, this was an outpatient-oriented survey in a primary care setting, so the findings can be broadly applied with greater confidence. The study showed Maxmarvil had long-term efficacy up to 1 year, and it was possible to assess an accurate drug response due to the high drug compliance. Since all the centers measured BMD with DEXA, a standardized efficacy assessment was feasible.
The present study had several limitations. First of all, as our study analysis included the subjects who followed the study protocol completely, the efficacy of Maxmarvil could be exaggerated. In addition, this study did not include a placebo-controlled group. We could only specify the result by absolute changes in BMD before and after treatment. Therefore, we could not ascertain the direct relationship between Maxmarvil efficacy and fracture reduction. Although opinions differ as to whether fracture risk reduction is attributable to BMD improvement, major clinical trials have demonstrated that alendronate treatment reduced vertebral and non-vertebral fractures by 48% and 47%, respectively.25
Moreover, the relationship between BMD increase and fracture risk reduction is not proportional; a small BMD improvement has been found to cause a remarkable reduction in fracture risk.27
Although our study did not include a control group, by considering the absolute changes in BMD after treatment, we can assume that it would have positive effects on fracture reduction.
In conclusion, this survey of postmenopausal women with osteoporosis in a primary care setting found that Maxmarvil was efficacious, safe, and well tolerated.