The impact of vitamin D status on changes in bone mineral density during treatment with bisphosphonates and after discontinuation following long-term use in post-menopausal osteoporosis

Abstract

Background: It is still unclear whether addition of calcium/vitamin D supplements leads to an incremental benefit in patients taking bisphosphonates and whether achievement of serum level of 25 (OH) vitamin D of at least 70 nmol/L has an impact on the skeletal response to bisphosphonates. Moreover the maintenance of BMD after bisphosphonates withdrawal with the continuation of calcium/vitamin D supplements only, remains uncertain. The aims were to assess the impact of vitamin D status on changes in bone mineral density (BMD) in firstly patients with post-menopausal osteoporosis on bisphosphonates and secondly following discontinuation of bisphosphonates after long-term use.

Methods: Two patient groups were recruited. The first study population comprised of 112 women treated with a bisphosphonate. The second study population consisted of 35 women who had been on bisphosphonates for > 5 years in whom the treatment agent was discontinued. Baseline BMD, changes in BMD following treatment, duration of treatment, serum 25 (OH) vitamin D, parathyroid hormone (PTH), urine C-terminal telopeptides of type 1 collagen (CTX) were obtained on the study participants.

Results: In the first study group, subjects with serum vitamin D concentrations (> 70 nmol/L) had a significantly lower serum PTH level (mean [SEM] 41 2 ng/L). PTH concentrations of 41 ng/L or less was associated with a significantly higher increase in BMD at the hip following treatment with bisphosphonates compared to patients with PTH > 41 ng/L (2.5% [0.9] v/s -0.2% [0.9], P = 0.04). In the second study group, discontinuation of bisphosphonate for 15 months after long-term treatment did not result in significant bone loss at the lumbar spine and total hip, although a trend towards gradual decline in BMD at the femoral neck was observed.

Conclusion: the data suggest that optimal serum 25 (OH) vitamin D concentration may lead to further reduction in bone loss at the hip in patients on bisphosphonates. A prospective controlled trial is needed to evaluate whether the response to bisphosphonates is influenced by vitamin D status. BMD is preserved at the lumbar spine and total hip following discontinuation of bisphosphonate for a short period following long-term treatment, although a gradual loss occurs at the femoral neck.

Figure 1

Percentage change in BMD from baseline during bisphosphonate treatment at the lumbar spine and total hip in the study population divided into 2 groups based on their serum PTH concentration (cut-off value: 41 ng/L). A significant difference in % change in BMD at the hip was observed between the 2 groups. Values are shown as the mean [SEM], * p < 0.05.

Figure 2

Percentage change in BMD from baseline during bisphosphonate treatment at the lumbar spine and total hip in the study population divided into 2 groups based on their serum 25 (OH) D concentration (cut-off value: 70 nmol/L). The % change in BMD at the hip was less in the group with sub-optimal vitamin D. Values are shown as the mean [SEM], # p = 0.08.

Figure 3

The relationship between percentage change in BMD at the Lumbar spine and PTH concentrations.

Figure 4

The relationship between percentage change in BMD at the total hip and PTH concentrations.

Figure 5

Changes in BMD at the lumbar spine following discontinuation of bisphosphonates for 12–18 months after long-term use.

Figure 6

Changes in BMD at the hip following discontinuation of bisphosphonates for 12–18 months after long-term use.

Figure 7

BMD changes at the femoral neck from baseline in the patients at and after discontinuation of long-term bisphosphonates. A downward trend in FN BMD was observed after bisphosphonate withdrawal (* p = 0.094).