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 (ASBMR)

Toronto, Ontario / October 15-19, 2010

By the year 2050, hip fractures are expected to increase by two- to threefold from current incidence rates. The morbidity and mortality associated with hip fracture is high: 1 in 5 patients die within the first year of sustaining their fracture and half do not return to previously independent living nor walk independently after the fracture.

As discussed here at ASBMR by Dr. Mary Bouxsein, Harvard Medical School, Boston, Massachusetts, 90% of hip fractures are due to a fall and more specifically a fall to the side. While strong in walking and standing, the femur is 3.5 times weaker in a fall configuration and rendered weaker still as people sustain bone and muscle loss with age. Paradoxically, age-standardized hip fracture rates have fallen in many countries in the West since the mid-1990s.

Between 1992 and 2002, hip fracture rates decreased by approximately 23% in a cohort of 80- to 84-year olds enrolled in the SOF (Study of Osteoporotic Fractures). This may be explained in part by a 3-kg weight gain observed in the cohort over the same decade since increased use of OP treatments in the SOF cohort could only account for about one-quarter of declining hip fracture rates according to Dr. Steven Cummings, California Pacific Medical Center Research Institute, San Francisco.

However, atypical femoral fractures (AFFs) may be increasing, possibly as a result of long-term bisphosphanate (BP) use. In a special Task Force report on AFFs, co-chair Dr. Elizabeth Shane, Columbia University, New York, and colleagues, cautioned that AFFs are extremely rare, accounting for less than 1% of all hip and thigh fractures overall. In their review of 310 cases of AFF, they noted that 94% of patients had been exposed to BPs, most for more than 5 years.

Prevalence data provided by Dr. Bo Abrahamsen, Copenhagen University Hospital Gentofte, Denmark, confirmed that AFFs are rare. As a high-end estimate, the medical community could expect 5 AFFs to occur for every 1000 women with a fracture risk similar to participants in FIT (Fracture Intervention Trial) treated with a BP for 5 years. Conversely, BPs prevent far more fractures at between 35 and 50 non-vertebral fractures (VFs) and 50 to 115 VFs in the same 1000 women.

HORIZON Extension Study

Three years after randomizing patients to zoledronic acid (ZA) or placebo, women in the original HORIZON cohort were eligible for the extension study provided they had received all 3 annual infusions of ZA. A total of 1233 women were randomized to either ZA for another 3 years (Z6 group) or to placebo (Z3P3 group). The primary end point was percentage change in femoral neck bone mineral density (BMD) at year 6 relative to year 3.

At the end of the 3-year extension study, mean femoral neck BMD remained constant from the extension baseline in the Z6 group whereas it dropped slightly in the Z3P3 controls, for a between-group difference of 1.04% at year 6 (P=0.009) (both groups remained well above pretreatment levels, however). Adverse event (AE) rates were similar in both groups.

Thus, after 3 years of ZA treatment, it may be beneficial for some women, particularly those with a high VF risk, to continue on annual active therapy, the authors concluded.

Benefits of Recombinant Parathyroid Hormone in Elderly Women

Under lead author Walsh et al., investigators explored the effect of teriparatide, a recombinant form of parathyroid hormone (PTH), on the incidence of fracture, quality of life and back pain in an elderly subgroup of women enrolled in EFOS (European Forsteo Observation Study). Unlike anti-resorptive agents which stop high bone turnover, teriparatide is an anabolic and creates new bone tissue.

A total of 298 women =75 years old were included in the analysis. Women received daily teriparatide injections for up to 18 months, after which it was discontinued, and received a BP or other OP therapies. During 36 months of follow-up, 14.8% of the cohort sustained at least 1 fracture.

Nevertheless, the fracture incidence declined from a baseline rate of 4.4% (0 to 6 months), to 2.9% (18 to 24 months) and to 0.9% (30 to 36 months). There was an 80% decrease in the odds of women sustaining a fracture between the first 6 month-period and months 30 to 36 (P<0.009). The percentage of patients reporting daily back pain decreased from over two-thirds (~68%) at baseline to approximately one-third (~34%) at 6 months and to slightly over 22% at month 36.

Similarly, the percentage of reported severe back pain dropped from about half at baseline to approximately 20% at 6 months and approximately 11% at month 18 and month 36.

Underlining the severity of the disease and associated back pain treated in this study, some 80% of patients remained adherent to the daily injection regimen.

Vitamin D and Overall Health

Evidence supporting a protective effect of vitamin D in either cancer or CV disease (CVD) is not consistent and most studies show no significant association. As discussed by Dr. JoAnn Mason, Professor of Medicine, Harvard Medical School, Boston, laboratory evidence indicates that vitamin D inhibits cell proliferation, inflammation and angiogenesis, which could have a positive effect in cancer. The best evidence supporting a protective benefit from 25-hydroxyvitamin D or 25-(OH)-D appears for colorectal cancer. In other cancers, its effects are modest and, there is concern that it may increase disease risk in pancreatic cancer.

Vitamin D mechanisms that have the potential to protect patients from CVD have again been demonstrated in the laboratory; while encouraging, hard data are scarce in humans. A large-scale randomized trial, VITAL, is currently underway and aims to study 20,000 men and women who will receive vitamin D3 2000 IU/day or placebo, then omega-3 fatty acids or placebo. The primary objective of VITAL is to evaluate whether vitamin D3 has any effect on total and site-specific cancer outcomes as well as CV outcomes.

Sarcopenia or age-related loss of skeletal muscle mass is increasingly prevalent with age, especially among women. Reduction in muscle mass leads to corresponding bone loss and subsequent falls and fractures. In a meta-analysis of 12 randomized controlled trials (RCTs), Dr. Heike Bischoff-Ferrari, University of Zurich, Switzerland, and colleagues showed that only the highest quartiles of vitamin D ranging from 792 to 2000 IU/day reduced fracture risk, 14% for non-VFs and 30% for hip fractures.

These and related findings underscore the need for higher 25-(OH)-D levels for fracture and fall prevention (namely, 75 to 100 nmol/L)—for most adults, 800 IU/day of vitamin D3 should suffice. Dr. Christopher Kovacs, Professor of Medicine, Memorial University, St. John’s, Newfoundland, reviewed the literature and concluded that maternal requirements for vitamin D do not change during pregnancy or lactation but that a maternal 25-(OH)-D levels >50 nmol/L should ensure the fetus has adequate levels.

Whatever benefits vitamin D provide to human health, it does not apparently abrogate the negative impact of calcium supplementation on myocardial infarction (MI) risk. In a re-analysis of the Women’s Health Initiative, Dr. Ian Reid, University of Auckland, New Zealand, and colleagues calculated that for non-obese women, those randomized to calcium (1 g) vitamin D (400 IU) supplement had a 28% increased risk for a revascularization procedure and a 24% increased risk for the composite end point of total MI, CHD death and revascularization (obese women did nor share this increased risk).

Consequently, investigators felt that the role of calcium supplementation ± vitamin D in OP prevention and treatment warrants reassessment.

Summary

New insights into the preservation of bone and muscle health offer the potential to reduce fracture risk among the most vulnerable patients, namely the elderly. Key to this is ensuring adequate amounts of vitamin D but fracture prevention through suppression of high bone turnover with BPs is equally vital. In severe OP or in non-response, anabolic agents such as teriparatide are useful in creating new bone. With goals of fracture prevention and maintenance of independence in our elderly populations, it is reassuring that there are a number of therapeutic options with which to better manage OP.

Based on scientific presentations from the ASBMR meeting selected by a review committee headed by Dr. Kendler, in keeping with the principles of accreditation. Both Dr. Kendler and Dr. Josse have edited and approved the content and related slides as educational material.

This event is approved for up to 0.5 CME study credits by the Centre for Continuing Health Professional Education (CCHPE). The Centre for CCHPE, Faculty of Medicine, McGill University is fully accredited by the Committee on Accreditation of Canadian Medical Schools (CACMS), and through the CACMS is accredited to award AMA PRA category 1 credits. This program meets the accreditation criteria of the College of Family Physicians of Canada for MAINPRO-M1 credits. Members of the American Academy of Family Physicians are eligible to receive credit hours for attendance at this meeting due to a reciprocal agreement with the College of Family Physicians of Canada.

Each physician should claim only those hours of credit that he/she actually spent at the educational activity.