Osteoporosis is a skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, which consequently increase bone fragility and the susceptibility to fracture 1. Osteoporosis strikes one in four women over the age of 50 years 2. There are over 20 000 osteoporosis-related hip fractures in Canada annually. The mortality associated with hip fractures exceeds 25% at one year, with nearly one quarter of survivors requiring institutionalization in a long-term care facility 3.

Bisphosphonates are indicated in the prevention and treatment of Osteoporosis, as they are potent inhibitors of bone resorption. Clinical trials in primary Osteoporosis have provided conclusive evidence that in most patients therapy with this class of drug leads to improvement in bone mass and a reduction in subsequent fractures 45678910111213141516171819.

Despite treatment with a bisphosphonate, bone mineral density (BMD) continues to decline in up to 15% of etidronate users and 5% of alendronate users 413. As a consequence, vitamin D may be recommended as adjunctive therapy in addition to increased calcium intake in those who do not to respond to bisphosphonate therapy. The vitamin D metabolite 1,25-dihydroxy vitamin D (calcitriol) is required for the active intestinal absorption of calcium and plays in concert with the parathyroid hormone (PTH), an important role in releasing calcium from bone and regulating plasma calcium 20. Vitamin D deficiency is a risk factor for Osteoporosis 21222324. Moreover, daily supplementation with vitamin D and calcium has been shown to reduce bone loss at the spine and femoral neck as well as the prevalence of non-vertebral fractures 252627.

While a large number of randomized trials have evaluated the efficacy of bisphosphonate treatment with concurrent vitamin D (in doses varying between 125 to 500 IU) 41628293031, the incremental benefit of vitamin D in patients taking bisphosphonates is uncertain. Therefore, from data that were collected from the Canadian Database of Osteoporosis and Osteopenia (CANDOO) patients 32, we performed a 2-year observational cohort study to determine the impact of prescribed vitamin D supplements on BMD in osteoporotic patients who had not responded to bisphosphonates and calcium therapy alone.

Patient characteristics are presented in Table 1. Overall, 449 patients were identified, 159 patients received a bisphosphonate and vitamin D while 290 received bisphosphonate therapy. Due to missing data, lumbar spine BMD was available for 155 (BISVITD) and 282 (BIS) patients, whereas femoral neck BMD was available for 156 and 280 patients from each treatment group, respectively. The 12 patients for whom lumbar spine data were missing had a higher BMI (29.1 vs. 25.9 kg/m², p = 0.020) and consumed more hypnotics (33% vs 10%, p = 0.030) as compared with patients that had complete lumbar spine data. Furthermore, the 13 patients with missing femoral neck data were more likely to have received systemic steroids (46% vs 18%, p < 0.010), tamoxifen (10% vs 3%, p < 0.001) and fluoride (30% vs 8%, p = 0.005); less likely to receive anti-epileptics (10% vs 0.9%, p = 0.006); and had a higher serum ALP than the group with complete femoral neck data (120.8 vs 90.9 mmol/L, p = 0.018).

Of the patients evaluated in the study, 94% were women. The cohort was relatively elderly, with a mean age of 74.6 years (standard deviation = 5.6 years). There were statistically significant differences between the groups at baseline with respect to age, BMI, type of bisphosphonate, calcium supplementation and lumbar BMD. There was no difference in total calcium intake. There were significant differences in exposure to immune suppressing and lipid lowering agents, though 0.7% and 1% of all patients respectively had received such medications. Serum 25(OH)D levels were not different between the groups, but were available for 51 treatment and 115 control patients only (Table 1).

BMD continues to decline in 5 to 15% of patients with osteoporosis despite treatment with etidronate or alendronate 413. These patients often receive supplementation with vitamin D, though evidence to support the value of this intervention has been lacking. In our analysis of patients not responding to stable bisphosphonate therapy, we demonstrated that the concurrent use of vitamin D (1000 lU/d) was associated with an increased lumbar spine (1.45%) and femoral neck BMD (1.15%) in those who had previously experienced a decline in BMD while on bisphosphonate therapy alone. In addition, no significant differences were found between those who initially responded to bisphosphonate therapy versus non-responders following treatment. This suggests that vitamin D supplementation may be an effective concurrent medication in those who have not responded to bisphosphonate therapy.

The power of the study to detect a 1.15% (standard deviation= 4%) change in femoral neck bone density from baseline to the second-follow-up visit in the 156 patients was approximately 95%. The absence of a statistically significant response to vitamin D at the femoral neck suggests that the lumbar spine and femoral neck may respond differently to vitamin D. Differences in bone density response between the lumbar spine and the femoral neck have been observed in other studies 3334.

In this study, the improvement in BMD occurred despite no significant difference in serum 25(OH)D levels between the two treatment groups at baseline, and no relationship between baseline levels and response to prescribed vitamin D was observed. The low baseline 25(OH)D is consistent with previous observations of vitamin D deficiency in elderly persons 35, and suggests that the observed increases in BMD may partially reflect improved nutritional status.

The principal limitation of this observational study was that patients were not randomized into their respective treatment groups. The majority of patients in the intervention group were selected based on declining BMD after one year of treatment. Thus, differences between the groups were found at baseline. In addition, as the treatment group was defined by a decline in BMD after one year, regression to the mean may partially explain the improvement in BMD measured at the second follow-up 36. The absence of blinding may have motivated patients not responding to bisphosphonates to adhere more rigorously to recommended dietary and lifestyle recommendations, confounding the effect on BMD attributed to vitamin D. Finally, sample size limitations prevent generalizability of the results to male patients and those receiving alendronate.

In summary, in elderly patients with osteoporosis who are not responding to bisphosphonates, concomitant use of vitamin D may improve BMD of the lumbar spine. Clearly, the hypothesis that vitamin D improves BMD in patients receiving bisphosphonates needs to be verified in a prospective controlled trial.

None Declared.