Vitamin D Status on Changes in Bone Mineral Density During Treatment with Bisphosphonates

BMC Musculoskeletal DisordersVol 8
An Open Access research article from BMC
Published 10 January 2007

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.

Background
Bisphosphonates are widely used in the treatment of osteoporosis and prevention of osteoporosis-related fractures. The efficacy of these anti-resorptive agents has been extensively studied in several randomised controlled trials [1,2]. In all published clinical trials, calcium and vitamin D supplements have also been used with the bisphosphonates as adjunctive therapy. Large scale studies have shown that vitamin D supplementation between 700 and 800 I.U/day leads to a reduction in the risk of hip fracture and non-vertebral fractures by 30% in adults older than 65 years [3], although recent trials have shown that vitamin D, either alone or in combination with calcium supplementation was ineffective in the primary or secondary prevention of fractures in community-dwelling older people [4,5]. However in the RECORD study [4], concentrations of 25 (OH) vitamin D were measured only in a very small subset of the patients. Therefore the vitamin D status of the majority of participants was unknown. Low serum concentrations of vitamin D is widespread in the U.K [6] and moderate vitamin deficiency in older people results in poor bone and muscle strength [7,8]. Serum 25 (OH) vitamin D concentrations that correlate with clinically significant effects on muscle function and fracture prevention is at least 70 nmol/L [9]. 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 vitamin D of at least 70 nmol/L has an impact on the skeletal response to bisphosphonates.

Bisphosphonates including Alendronate, Etidronate and Risedronate have a long retention time in bone and there are some concerns about their long-term effects on skeletal mineralization [10]. Recent studies, including the fracture intervention trial have shown that Alendronate, administered for up to 10 years is safe and has continued benefit on the skeleton [11]. The data also show that discontinuation of long-term (5 years or more) Alendronate therapy results in minimal bone loss at the spine, suggesting persistence of Alendronate's effects on bone. However discontinuation of Alendronate seems to lead to gradual loss of effect at the femoral neck and hip [11] although data outside the confines of the randomised controlled trial setting data are lacking. Thus the partial maintenance of bisphosphonates effects after their withdrawal with the continuation of calcium/vitamin D supplements only remains uncertain in routine clinical practice. This is of practical value particularly in patients where compliance is an issue.

The aim of the study was to (1) determine the effect of optimum serum concentrations (> 70 nmol/L) of 25(OH) vitamin D on the skeletal response in patients treated with bisphosphonates and (2) assess changes in bone mineral density (BMD) following 12–18 months withdrawal of Etidronate or Alendronate in long-term users (> 5 years) with the continuation of calcium/vitamin D supplements in post-menopausal osteoporosis, in the practical setting of a metabolic bone clinic service.

Methods

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