Elsevier

Bone

Volume 51, Issue 1, July 2012, Pages 54-58
Bone

Original Full Length Article
25 hydroxyvitamin D serum levels influence adequate response to bisphosphonate treatment in postmenopausal osteoporosis

https://doi.org/10.1016/j.bone.2012.03.026Get rights and content

Abstract

It remains unclear whether vitamin D sufficiency optimizes response to bisphosphonate (BP) treatment in postmenopausal osteoporosis. We evaluated the role and possible mechanisms of vitamin D in adequate response to standard BP treatment for postmenopausal osteoporosis.

Methods

We included 120 postmenopausal osteoporotic women (aged 68 ± 8 years) receiving BP (alendronate or risedronate) at their annual follow-up, performing complete anamnesis, including treatment adherence, use of vitamin D supplements, and previous falls and fractures during the last year. We analyzed the evolution of bone mineral density (BMD) during this period and serum PTH and 25 hydroxyvitamin D (25(OH)D) and urinary NTx levels. Patients were classified as inadequate responders to antiosteoporotic treatment based on BMD loss > 2% and/or the presence of fragility fractures during the last year.

Results

Thirty percent of patients showed inadequate response to BP treatment, with significantly lower levels of 25(OH)D (22.4 ± 1.3 vs. 26.6 ± 0.3 ng/ml, p = 0.01), a higher frequency of 25(OH)D levels < 30 ng/ml (91% vs. 69%, p = 0.019) and higher urinary NTx values (42.2 ± 3.9 vs. 30.9 ± 2.3 nM/mM, p = 0.01). Patients with 25(OH)D > 30 ng/ml had a greater significant increase in lumbar BMD than women with values < 30 ng/ml (3.6% vs. 0.8%, p < 0.05). The probability of inadequate response was 4-fold higher in patients with 25(OH)D < 30 (OR, 4.42; 95% CI, 1.22–15.97, p = 0.02).

Conclusions

Inadequate response to BP treatment is frequent in postmenopausal women with osteoporosis as is vitamin D insufficiency, despite vitamin D supplementation. Maintenance of 25(OH)D levels > 30 ng/ml is especially indicated for adequate response to BP treatment.

Highlights

► Inadequate response to bisphosphonate treatment is not uncommon in postmenopausal women with osteoporosis. ► Vitamin D insufficiency is frequent, despite vitamin D supplementation. ► Maintenance of vitamin D levels > 30 ng/ml is indicated for adequate response to BP treatment.

Introduction

Vitamin D deficiency is a common condition in postmenopausal women, especially in those with osteoporosis, being reported in more than 50% of these individuals [1]. In some series this finding has also been associated with the severity of osteoporosis [2]. Indeed, depending on the serum levels considered, we have recently observed low serum 25 hydroxyvitamin D (25(OH)D) values in 57% to 82% of women with untreated postmenopausal osteoporosis. This factor was associated with a higher prevalence of vertebral fractures and lower bone mass in these patients [3], further indicating the convenience of maintaining appropriate serum levels of this vitamin in this population. Although there is no clear definition related to the 25(OH)D levels required in osteoporotic subjects, there is an emerging consensus suggesting that the optimal 25(OH)D serum concentrations in these individuals should be over 30 ng/ml, with lower levels being indicative of vitamin D insufficiency [4], [5], [6]. This lower concentration does not only affect bone metabolism, by a secondary increase in parathyroid hormone (PTH) secretion, but also involves muscle function [7], [8]. Thus, vitamin D deficiency has been associated with impaired muscle function and, consequently, with an increase in the risk of falls, thereby contributing to the development of fractures in this population [8]. There are several studies indicating the convenience of maintaining appropriate 25(OH)D levels in the osteoporotic population, however, few have analyzed the effect of vitamin D insufficiency on the efficacy of antiosteoporotic treatment. Indeed, inadequate response to antiosteoporotic treatment, mainly with bisphosphonates (BP), has been reported in 18–35% of the patients, depending on the definition of the nonresponse criteria [9], with lack of vitamin D supplementation being an independent determinant of inadequate response to antiresorptive treatment in some studies [10], [11]. Nevertheless, it is not well known whether vitamin D insufficiency may contribute to a lower response to antiresorptive treatment, and the serum 25(OH)D levels required in these individuals remain to be defined.

Therefore, the aim of this study was to evaluate the role and possible mechanisms of vitamin D in the inadequate response to the standard treatment for postmenopausal osteoporosis with BP.

Section snippets

Study design

This is a cross-sectional study which consecutively included 120 women from 48 to 89 years of age (mean ± SEM 68.8 ± 0.8 years) diagnosed with postmenopausal osteoporosis who had been receiving treatment with BP (alendronate or risedronate) for at least 1 year. Postmenopausal women with osteoporosis attending an outpatient Metabolic Bone Diseases Unit who fulfilled the inclusion criteria for the study were invited to participate at their annual follow-up visit.

The main inclusion criteria were: having

Results

The characteristics of the study population are shown in Table 1. Most patients were treated with alendronate (63% of women were taking weekly alendronate vs. 37% weekly risedronate). Ninety percent of the patients received additional supplementation with calcium and vitamin D (57% with doses of 500/400 IU/day and 33% with doses of 1000 mg/800 IU/day). Adherence to the treatment was considered optimal in 76% of patients. Nearly one third (28%) of the patients presented at least one fall during the

Discussion

The results of this study indicate that 25(OH)D serum levels influence adequate response to BP treatment in postmenopausal osteoporosis. Indeed, we observed that patients classified as inadequate responders to BP treatment, by BMD loss or the development of fractures, presented significantly lower levels of 25(OH)D and increased urinary NTx values, thereby suggesting an increase in bone turnover and, consequently, in bone loss in these patients. In addition, patients with 25(OH)D serum levels

Acknowledgments

We would also like to thank Abiguei Torrents and Ferran Torres (Biostatistics and Data Management Platform, IDIBAPS, Hospital Clinic Barcelona) for their statistical support. This work was supported in part by a grant from Merck Sharp & Dohme.

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    1

    Drs. Peris and Martínez-Ferrer contributed equally to this work.

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