Reports

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

6th European Congress on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis

Vienna, Austria / March 15-18, 2006

According to Dr. Heike Bischoff-Ferrari, Department of Rheumatology and Institute for Physical Medicine, University Hospital, Zurich, Switzerland, “Vitamin D [Vit D] supplementation combats nonvertebral fracture risk in older persons through both a moderate increase in bone mineral density and a reduction in the risk of falling. Two meta-analyses suggest that Vit D should reduce the risk of falling by more than 20% and reduce the relative risk for first hip or any other nonvertebral fracture by about a quarter.”

The Essential Role of Vit D

Dr. Bischoff-Ferrari said a recent study demonstrated that 64% of postmenopausal women with osteoporosis have serum 25-hydroxyVit D3 (25[OH]D) levels <75 nmol/L. A large US national survey of healthy, home-dwelling ambulatory persons 60 years of age or older suggests that no more than 33% of Caucasians and only 12% of the Black population had 25(OH)D levels >80 nmol/L. This is important because Vit D is essential for maintaining calcium homeostasis and bone health by increasing intestinal calcium absorption and regulating bone turnover. Vit D inadequacy leads to disturbances of calcium and phosphorus homeostasis, secondary hyperparathyroidism leading to increased bone resorption and turnover, osteoporosis and high fracture risk.

Beyond the benefits of improved calcium absorption on bone, epidemiologic, clinical and laboratory studies suggest a direct effect of Vit D on muscle strength. The effect of Vit D on balance and muscle in a trial of elderly women given 800 IU of Vit D plus 200 mg of calcium vs. calcium alone revealed a statistically significant 9% decrease in body sway within two months. Dr. Bischoff-Ferrari’s study among frail institutionalized elderly women with very low serum 25(OH)D who were given those same comparative regimens reported a 5% to 11% improvement in muscular strength and function and a significant 49% reduction in the rate of falls.

In a pooled analysis of hip fracture results from five high-quality trials and seven high-quality trials for non-vertebral fractures, Dr. Bischoff-Ferrari found that patients given 700 to 800 IU of Vit D achieved a 26% reduction in the risk of hip fractures, with the number of patients needed to treat to prevent one hip fracture being 45. The reduction of any non-vertebral fractures was 23% and number needed to treat was 27. The efficacy of treatment increased as 25(OH)D levels rose, and the meta-regression was significant for both hip and non-vertebral fractures when levels did increase. Based on the NHANES study, it is important to achieve 25(OH)D levels of at least 49 nmol/L, but optimally 90 to 100 nmol/L, she stressed.

Addressing Unmet Medical Needs

Dr. Silvano Adami, University of Verona Medical School, Italy, told delegates that the current epidemic of Vit D inadequacy among women with osteoporosis is attributable to reduced exposure to sunlight, decreased dietary intake of Vit D and age-related reductions in the ability of the skin to synthesize Vit D. Moreover, adherence to daily oral supplements of calcium and Vit D is generally below 40%, which also contributes Vit D inadequacy, he added.

Noting the dissimilar outcomes of various bisphosphonates in osteoporosis therapy, Dr. Adami said that there is extensive data on the efficacy of alendronate therapy for lowering osteoporotic fracture risk. A recent meta-analysis, for example, confirmed that the average decrease in vertebral and hip fracture rates with the compound was about 55%, while increasing bone mineral density by 7% to 9% at the spine and by 5% to 8% at the hip and providing significant reductions in bone turnover. The anti-fracture efficacy of alendronate appeared to be maintained over a wide range of age groups.

Dr. Adami underlined the importance of fracture prevention by citing pooled data from more than 20 studies which recorded the relative risk of death at three months following hip fracture to be 5.06 and still 1.44 at five years’ post-fracture. A novel formulation, the first osteoporosis therapy of this type, combines alendronate, which has demonstrated efficacy in reducing the risk of hip and spine fractures, with a single weekly dose of Vit D. Dr. Adami believes alendronate 70 mg with colecalciferol (Vit D3) 2800 IU in a single tablet given once weekly addresses a critical unmet medical need. In a 652-patient study, postmenopausal women treated with the once-weekly tablet achieved a significant 26% increase in Vit D levels compared to those treated with the bisphosphonate alone after 15 weeks (P<0.001). The combination significantly reduced Vit D inadequacy by 91% and the proportion of patients with 25(OH)D levels <37.5 nmol/L by 64% (P<0.001).

“The dose was well tolerated and is appropriate for most women at risk of Vit D deficiency,” Dr. Adami told delegates. “More Vit D may be necessary in very elderly persons,” he added. Although the tolerable upper intake level for adults has been set at 2000 IU/day in the US, no toxicity has been observed with daily intake of up to 10,000 IU and no hypercalcemia or renal stones were reported in a trial using 5600 IU weekly, even though sun exposure and additional Vit D supplementation was allowed.

Inadequacy a Canadian Issue

“While concurrent Vit D and calcium inhibit resorption, they do not replace bone,” he noted. “But studies show that once calcium and vitamin intake is corrected, alendronate increases bone density and strength and improves mineralization. Bone resorption may be reduced 40% to 60% and fracture reduced by 50%.”

Supporting Dr. Olszynski’s view of low Vit D levels in the Canadian population, researchers at McGill University, Montreal, Quebec, assessed the baseline distribution of 25(OH)D levels in 449 men and postmenopausal women who were receiving 400 IU or less Vit D supplementation daily (~25%), or were not being treated for osteoporosis, at entry into the FACTOR study, which was carried out across eight provinces.

McGill University co-investigator Dr. Andrew C. Karaplis offered that interim results indicate a high prevalence of Vit D inadequacy. He reported that the mean overall 25(OH)D level was 66.3 nmol/L. Almost two-thirds of patients (63.7%) had levels <75 nmol/L, the level associated with increased serum parathyroid hormone. Nearly one-half of participants (45%) reported levels <62.5 nmol/L and 27.4% of patients had levels <50 nmol/L. Among the latter were 1.8% of the group with 25(OH)D serum concentrations <22.5 nmol/L and 12.7% with concentrations <37.5 nmol/L. Neither age nor gender influenced the prevalence of Vit D insufficiency.

Reporting on prescription Vit D use among patients taking antiresorptive agents in Canada, Dr. David Hanley, University of Calgary Health Science Centre, Alberta, said that even though current guidelines recommend the use of Vit D with antiresorptive agents, the majority of osteoporotic patients in Canada still do not take Vit D. Among 46,226 antiresorptive users (90.3% women) in this study, only 37.1% were given a prescription during one-year follow-up. On average, patients had a supply of Vit D for only 55% of the days on their antiresorptive regimens.

Summary

As reported by the authors of this survey, even with a diagnosis of osteoporosis requiring the use of antiresorptive agents, a substantial number of patients are not taking Vit D, indicating a considerable gap in optimizing therapy. Treatments that guarantee the use of Vit D along with antiresorptive agents can potentially address this treatment gap, they concluded.