Alan Tenenhouse

Predictive Value of BMD for Hip and Other Fractures.

The relationship between BMD and fracture risk was estimated in a meta‐analysis of data from 12 cohort studies of ∼39,000 men and women. Low hip BMD was an important predictor of fracture risk. The prediction of hip fracture with hip BMD also depended on age and z score.

INTERMITTENT ETIDRONATE THERAPY TO PREVENT CORTICOSTEROID- INDUCED OSTEOPOROSIS

BACKGROUND AND METHODS Osteoporosis is a recognized complication of corticosteroid therapy. Whether it can be prevented is not known. We conducted a 12-month, randomized, placebo-controlled study of intermittent etidronate (400 mg per day for 14 days) followed by calcium (500 mg per day for 76 days), given for four cycles, in 141 men and women (age, 19 to 87 years) who had recently begun high-dose corticosteroid therapy. The primary outcome measure was the difference in the change in the bone density of the lumbar spine between the groups from base line to week 52. Secondary measures included changes in the bone density of the femoral neck, trochanter, and radius and the rate of new vertebral fractures. RESULTS The mean (+/-SE) bone density of the lumbar spine and trochanter in the etidronate group increased 0.61 +/- 0.54 and 1.46 +/- 0.67 percent, respectively, as compared with decreases of 3.23 +/- 0.60 and 2.74 +/- 0.66 percent, respectively, in the placebo group. The mean differences between the groups after one year were 3.72 +/- 0.88 percentage points for the lumbar spine (P = 0.02) and 4.14 +/- 0.94 percentage points for the trochanter (P = 0.02). The changes in the femoral neck and the radius were not significantly different between the groups. There was an 85 percent reduction in the proportion of postmenopausal woman with new vertebral fractures in the etidronate group as compared with the placebo group (1 of 31 patients vs. 7 of 32 patients, P = 0.05), and the etidronate-treated postmenopausal women also had significantly fewer vertebral fractures per patient (P = 0.04). CONCLUSIONS Intermittent etidronate therapy prevents the loss of vertebral and trochanteric bone in corticosteroid-treated patients.

A meta-analysis of prior corticosteroid use and fracture risk

The relationship between use of corticosteroids and fracture risk was estimated in a meta‐analysis of data from seven cohort studies of ∼42,000 men and women. Current and past use of corticosteroids was an important predictor of fracture risk that was independent of prior fracture and BMD.

Smoking and fracture risk: a meta-analysis.

Smoking is widely considered a risk factor for future fracture. The aim of this study was to quantify this risk on an international basis and to explore the relationship of this risk with age, sex and bone mineral density (BMD). We studied 59,232 men and women (74% female) from ten prospective cohorts comprising EVOS/EPOS, DOES, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, Hiroshima and two cohorts from Gothenburg. Cohorts were followed for a total of 250,000 person-years. The effect of current or past smoking, on the risk of any fracture, any osteoporotic fracture and hip fracture alone was examined using a Poisson model for each sex from each cohort. Covariates examined were age, sex and BMD. The results of the different studies were merged using the weighted β-coefficients. Current smoking was associated with a significantly increased risk of any fracture compared to non-smokers (RR=1.25; 95% Confidence Interval (CI)=1.15–1.36). Risk ratio (RR) was adjusted marginally downward when account was taken of BMD, but it remained significantly increased (RR=1.13). For an osteoporotic fracture, the risk was marginally higher (RR=1.29; 95% CI=1.13–1.28). The highest risk was observed for hip fracture (RR=1.84; 95% CI=1.52–2.22), but this was also somewhat lower after adjustment for BMD (RR=1.60; 95% CI=1.27–2.02). Risk ratios were significantly higher in men than in women for all fractures and for osteoporotic fractures, but not for hip fracture. Low BMD accounted for only 23% of the smoking-related risk of hip fracture. Adjustment for body mass index had a small downward effect on risk for all fracture outcomes. For osteoporotic fracture, the risk ratio increased with age, but decreased with age for hip fracture. A smoking history was associated with a significantly increased risk of fracture compared with individuals with no smoking history, but the risk ratios were lower than for current smoking. We conclude that a history of smoking results in fracture risk that is substantially greater than that explained by measurement of BMD. Its validation on an international basis permits the use of this risk factor in case finding strategies.

A new approach to the development of assessment guidelines for osteoporosis

The diagnosis of osteoporosis is made from the measurement of BMD. DXA at the hip is the appropriate diagnostic site. Current clinical guidelines follow the principle that BMD measurements are indicated in individuals with risk factors for fracture and that treatment is recommended in those with a BMD below a critical value. In some countries reimbursement for the costs of treatment depend upon such thresholds for BMD. In Europe the critical value corresponds to a T-score of-2.5 SD, whereas in the USA less stringent criteria are used. It is evident, however, that fracture risk at any given T-score varies markedly according to age and other risk factors. This has led to the view that interventions should be targeted to those at high risk, irrespective of a fixed BMD threshold. In this sense, BMD is utlized as a risk assessment, since in many instances intervention thresholds will be less stringent than the diagnostic threshold. Thus, intervention thresholds need to differ from diagnostic thresholds and be based on fracture probabilities. A 10-year fracture probability appears to be an appropriate time frame. There are a number of problems to be overcome in the development of assessment guidelines. They need to take account of not only the risk of hip fracture but also that of other fractures which contribute significantly to morbidity, particularly in younger individuals. A promising approach is to weight fracture probabilities according to the disutility incurred compared with hip fracture probability. Account also needs to be taken of the large geographic variation in fracture probabilities worldwide. A further challenge for the future will be to identify risk factors that predict fracture with high validity in different regions of the world and their independent contributions, so that models of risk prediction can be constructed and ultimately validated in independent cohorts.

Estimation of the prevalence of low bone density in Canadian women and men using a population-specific DXA reference standard : The Canadian Multicentre Osteoporosis Study (CAMOS)

Abstract: The Canadian Multicentre Osteoporosis Study (CaMos) is a prospective cohort study which will measure the incidence and prevalence of osteoporosis and fractures, and the effect of putative risk factors, in a random sample of 10 061 women and men aged ≥25 years recruited in approximately equal numbers in nine centers across Canada. In this paper we report the results of studies to establish peak bone mass (PBM) which would be appropriate reference data for use in Canada. These reference data are used to estimate the prevalence of osteoporosis and osteopenia in Canadian women and men aged ≥50 years. Participants were recruited via randomly selected household telephone listings. Bone mineral density (BMD) of the lumbar spine and femoral neck were measured by dual-energy X-ray absorptiometry using Hologic QDR 1000 or 2000 or Lunar DPX densitometers. BMD results for lumbar spine and femoral neck were converted to a Hologic base. BMD of the lumbar spine in 578 women and 467 men was constant to age 39 years giving a PBM of 1.042 ± 0.121 g/cm2 for women and 1.058 ± 0.127 g/cm2 for men. BMD at the femoral neck declined from age 29 years. The mean femoral neck BMD between 25 and 29 years was taken as PBM and was found to be 0.857 ± 0.125 g/cm2 for women and 0.910 ± 0.125 g/cm2 for men. Prevalence of osteoporosis, as defined by WHO criteria, in Canadian women aged ≥50 years was 12.1% at the lumbar spine and 7.9% at the femoral neck with a combined prevalence of 15.8%. In men it was 2.9% at the lumbar spine and 4.8% at the femoral neck with a combined prevalence of 6.6%.

The influence of osteoporotic fractures on health-related quality of life in community-dwelling men and women across Canada.

Abstract: Health-related quality of life (HRQL) was examined in relation to prevalent fractures in 4816 community-dwelling Canadian men and women 50 years and older participating in the Canadian Multicentre Osteoporosis Study (CaMos). Fractures were of three categories: clinically recognized main fractures, subclinical vertebral fractures and fractures at other sites. Main fractures were divided and analyzed at the hip, spine, wrist/forearm, pelvis and rib sites. Baseline assessments of anthropometric data, medical history, therapeutic drug use, spinal radiographs and prevalent fractures were obtained from all participants. The SF-36 instrument was used as a tool to measure HRQL. A total of 652 (13.5%) main fractures were reported. Results indicated that hip, spine, wrist/forearm, pelvis and rib fractures had occurred in 78 (1.6%), 40 (0.8%), 390 (8.1%), 19 (0.4%) and 125 (2.6%) individuals, respectively (subjects may have had more than one main fracture). Subjects who had experienced a main prevalent fracture had lower HRQL scores compared with non-fractured participants. The largest differences were observed in the physical functioning (−4.0; 95% confidence intervals (CI): −6.0, −2.0) and role-physical functioning domains (−5.8; 95% CI: −9.5, −2.2). In women, the physical functioning domain was most influenced by hip (−14.9%; 95% CI: −20.9, −9.0) and pelvis (−18.1; 95% CI: −27.6, −8.6) fractures. In men, the role-physical domain was most affected by hip fractures (−35.7; 95% CI: −60.4, −11.1). Subjects who experienced subclinical vertebral fractures had lower HRQL scores than those without prevalent fractures. In conclusion, HRQL was lower in the physical functioning domain in women and the role-physical domain in men who sustained main fractures at the hip. Subclinical vertebral fractures exerted a moderate effect on HRQL.

Research Notes: The Canadian Multicentre Osteoporosis Study (CaMos): Background, Rationale, Methods

Relatively little is known about the factors in Canada which lead to osteoporosis and its concomitant fractures. The Canadian Multicentre Osteoporosis Study (CaMos) is a prospective cohort study which will estimate the incidence and prevalence of declining bone mass and fractures. The impact of osteoporosis in Canada will be assessed, including regional variation and the effect of various risk factors. The study will provide information for developing prevention programs. The cohort has been drawn from a random population-based sample of non-institutionalized men and women 25 years old or more and living within 50 km. of nine cities in Canada. Through telephone interviews 9,423 participants have been recruited. All answered an extensive questionnaire, and had physical measurements related to bone quality taken. This paper details the CaMos baseline and five-year follow-up protocol.

Vertebral fracture definition from population-based data: preliminary results from the Canadian Multicenter Osteoporosis Study (CaMos).

Abstract: The Canadian Multicenter Osteoporosis Study is a large population-based prospective study of osteoporosis in the Canadian population. The study involves 9424 subjects, both male and female, from nine centers and seven regions of Canada. Each subject completed an extensive interview to obtain medical, demographic and lifestyle information, and was examined by dual-energy X-ray absorptiometry of the spine and hip, ultrasound of the heel and, for subjects over 50 years of age, lateral spine radiographs. Spinal morphometry of the initial radiographs was performed to determine the prevalence of vertebral deformity. A method is utilized to extract reference norms for vertebral shape from a subset of the population data, which is then used to categorize any deformity within the whole data set. Using 3 standard deviations (SD) as a limit of normality, the male prevalence of 21.5% was similar to the female prevalence of 23.5%. Using 4 SD this reduced to 7.3% and 9.3% respectively. The younger men (50–59 years) showed a higher prevalence of deformity than the women and a lower increase of prevalence with age. In the older age group (over 80 years) the female prevalence of 45% compared with 36% for the men using 3 SD (grade 1) to define the limit of normality. The female group presented with more severe deformities on average than the male group. This continuing study will provide longitudinal information regarding the development of osteoporosis and associated risk factors which will eventually be of use to develop public health policies.

Peak Bone Mass From Longitudinal Data: Implications for the Prevalence, Pathophysiology, and Diagnosis of Osteoporosis

We estimated peak bone mass (PBM) in 615 women and 527 men aged 16 to 40 years using longitudinal data from the Canadian Multicentre Osteoporosis Study (CaMos). Individual rates of change were averaged to find the mean rate of change for each baseline age. The age range for PBM was defined as the period during which bone mineral density (BMD) was stable. PBM was estimated via hierarchical models, weighted according to 2006 Canadian Census data. Lumbar spine PBM (1.046 ± 0.123 g/cm2) occurred at ages 33 to 40 years in women and at 19 to 33 years in men (1.066 ± 0.129 g/cm2). Total hip PBM (0.981 ± 0.122 g/cm2) occurred at ages 16 to 19 years in women and 19 to 21 years in men (1.093 ± 0.169 g/cm2). Analysis of Canadian geographic variation revealed that the levels of PBM and of mean BMD in those over age 65 sometimes were discordant, suggesting that PBM and subsequent rates of bone loss may be subject to different genetic and/or environmental influences. Based on our longitudinally estimated PBM values, the estimated Canadian prevalences of osteoporosis (T‐score < –2.5) were 12.0% (L1–L4) and 9.1% (total hip) in women aged 50 years and older and 2.9% (L1–L4) and 0.9% (total hip) in men aged 50 years and older. These were higher than prevalences using cross‐sectional PBM data. In summary, we found that the age at which PBM is achieved varies by sex and skeletal site, and different reference values for PBM lead to different estimates of the prevalence of osteoporosis. Furthermore, lack of concordance of PBM and BMD over age 65 suggests different determinants of PBM and subsequent bone loss.