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.

PRIORITY PRESS - 32nd Annual Meeting of the American Society for Bone and Mineral Research

Toronto, Ontario / October 15-19, 2010

An adequate blood level of vitamin D (measured by serum 25[OH]D) is critical to bone health and associated outcomes including osteoporosis (OP), fractures and falls. Here at ASBMR, in a review of hospital charts across a number of specialties, Egli et al. (Abstract MO0326) found that out of 173 hip fracture patients 65 years and age or older, over half (51%) had severe vitamin D deficiency with 25(OH)D levels <30 nmol/L and 98% had levels below 75 nmol/L. Moreover, almost half (47.4%) had sustained one or more confirmed fractures in the 10 years preceding their hip fracture, and over one-third of them had sustained a non-vertebral fracture during this interval.

Dr. Heike Bischoff-Ferrari, University of Zürich, Switzerland, discussed a recent meta-analysis here at ASBMR of 12 randomized controlled trials of oral vitamin D supplementation involving more than 30,000 participants =65 years of age. Findings indicated that only the highest quartiles of vitamin D reduced non-vertebral fracture risk by 14% and hip fracture risk by 30%; the doses needed to attain these goals ranged between 792 and 2000 IU/day. Dr. Bischoff-Ferrari remarked that these doses would likely result in 25(OH)D levels of 75 nmol/L or more.

A sufficient level of vitamin D not only prevents fracture, she added; in fact, high supplemental doses of vitamin D3 have been shown to significantly reduce fall-related injuries in seniors =65 years. Their protective effects can be observed in less than 12 months. Conversely, low levels of 25(OH)D (<50 nmol/L) have been linked to a high risk of frailty in men although the association was weaker in women.

Findings from LASA (Longitudinal Aging Study Amsterdam) (Am J Clin Nutr 2006;84(3):616-22) indicated that patients with serum 25(OH)D levels <25 nmol/L had a 3.5 times greater risk of being admitted to a nursing home over a 6-year follow-up, compared with individuals with serum 25(OH)D levels >75 nmol/L.

On the other hand, very high doses of oral vitamin D3 appear to have a negative effect on falls and fractures in older women. According to VITAL D Study findings presented here by Sanders et al. (Abstract 1164), 2256 community-dwelling women, median age 76 years, were randomly assigned to receive a single oral dose of cholecalciferol 500,000 IU or placebo each autumn/winter for 3 to 5 years. Falls and fractures were ascertained for 4 to 6 years using monthly calendars. Details were confirmed by telephone interviews and fractures were radiologically confirmed. Results showed that the vitamin D group had more falls and fractures than placebo controls, at a fall rate of 83.4/100 person-years compared with 72.7/100 person-years. The increased rate of falling in the vitamin D group was also higher in the first 3 months following dosing and the cumulative incidence of first fall and first fracture were both increased in the vitamin D group.

Most experts now state that serum 25(OH)D levels of at least 75 nmol/L are necessary for the preservation of bone health. According to Dr. David Goltzman, National Principal Investigator, Canadian Multicentre Osteoporosis Study (CaMos) and Professor of Medicine, McGill University, Montreal, Quebec, vitamin D deficiency can be defined as 25(OH)D levels <25 nmol/L; a measurement between 25 and 50 nmol/L denotes insufficiency; and levels between 50 and 75 nmol/L are still suboptimal. Toxicity is presumed to occur when levels exceed 300 nmol/L.

Dr. Goltzman added that in a northern country such as Canada, patients might experience seasonal highs (summer) and lows (winter) of 25(OH)D levels. “Most adults need a vitamin D3 supplement because sunlight exposure and diet alone are not sufficient to maintain [an optimal] level throughout the year,” he confirmed. He suggested that a dose of 800 IU/day or 5600 IU/week is typically required to achieve serum 25(OH)D =75 nmol/L.

Canadian Treatment of Osteoporosis

To better understand how vitamin D levels are being assessed and managed in Canadian patients with OP, investigators led by Dr. Jonathan Adachi, Professor of Medicine, McMaster University, Hamilton, Ontario, collected practice profiles on 983 patients from 52 primary care practitioners and specialists. Among the patients evaluated, the mean bone mineral density (BMD) based on the most recent T-score was -2.15; 28% of the cohort had experienced a fragility fracture. Nearly 80% of the patients were receiving a bisphosphonate (BP) and 85% were also taking calcium and vitamin D supplements. A much smaller proportion, 8.5%, had also received glucocorticoid therapy for longer than 3 months.

Dr. Adachi reported here at the ASBMR that only about half of the patients in this study were taking an optimal dose (at least 5600 IU/week) of vitamin D. Among the approximately two-thirds of study subjects in whom serum vitamin D levels had been noted in the chart, approximately half had levels =80 nmol/L. Of those with low serum 25(OH)D levels, over three-quarters had been prescribed vitamin D 2800 IU/week. It is noteworthy that treating physicians did not recommend increased vitamin D supplementation in almost half of the patients with low serum 25(OH)D, even in those whose levels were <50 nmol/L. “Most physicians recommend calcium and vitamin D supplementation but vitamin D levels appear to be insufficient in half of patients, including over 40% of patients prescribed at least 2800 IU/week of vitamin D supplementation,” the authors commented.

In the same study, OP treatment regimens were evaluated in 769 patients. More than one-third (37%) had an unsatisfactory change in BMD. A similar percentage had unsatisfactory vitamin D levels. The authors concluded that having an unsatisfactory change in BMD was likely to be associated with unsatisfactory vitamin D levels.

Potential Benefits of a Combination Tablet

Persistence and compliance with vitamin D supplementation regimens can be low, which in turn impairs efficacy, as was demonstrated by the RECORD (Randomised Evaluation of Calcium Or vitamin D) Trial Group (Lancet 2005;365:1621-8) and by Jackson et al. (N Engl J Med 2006;354:669-83).

A combination tablet for once-weekly administration containing alendronate 70 mg and vitamin D3 5600 IU may ensure women with OP achieve optimal 25(OH)D levels. The tablet was compared with usual care for OP in an international, multicentre, open-label study led by Dr. Stuart Ralston, School of Molecular and Clinical Medicine, Western General Hospital, Edinburgh, UK. A total of 515 postmenopausal women (mean age 73 years) at increased risk of falls were randomly allocated to 1 of the 2 treatment arms for an initial 6-month study and a 6-month extension phase during which the subjects continued on their designated medication regimen. Most women in the usual-care group were taking some vitamin D, but the doses varied widely. In each study group, 228 women completed 1 year of treatment.

At baseline, the women in both study arms had 25(OH)D levels <20 ng/mL. After 6 months, significantly fewer patients receiving the once-weekly combination tablet had serum 25(OH)D <20 ng/mL (8.6% vs. 31% in the usual-care group). The difference remained significant at 12 months: 11.3% in the alendronate/vitamin D 5600 group vs. 36.9% in the usual-care group. The study participants receiving the combination tablet also had significantly greater gains in lumbar spine BMD (2.2% vs. 1.5%) and a trend toward greater gains in total hip BMD after 12 months of treatment. Significantly greater per cent decreases from baseline in urine N-telopeptides of type 1 collagen and in serum bone-specific alkaline phosphatase were also seen at both 6 and 12 months in the combination tablet-treated group than in the control group. The investigators observed no clinically meaningful differences in either safety or tolerability between the combination formulation and usual OP care.

Summary

Ensuring adequate vitamin D is both a preventive and—when combined with a BP—therapeutic measure for OP. Typically a dose of 800 IU/day is required to achieve optimal serum 25(OH)D levels of at least 75 nmol/L. Given the vast scope of discussions heard here during the ASBMR scientific sessions, this report focused on selected presentations regarding the use of vitamin D monotherapy and in combination with a BP.