Teriparatide and the risk of nonvertebral fractures in women with postmenopausal osteoporosis

Purpose

In the Fracture Prevention Trial, the risks of any nonvertebral fracture (relative risk [RR] 0.65, P = 0.04) and any fragility nonvertebral fracture (RR 0.47, P = 0.02) were significantly reduced in the teriparatide 20 μg/day (teriparatide) versus placebo group. The purpose of this analysis was to examine the efficacy of teriparatide versus placebo on a variety of other nonvertebral fracture outcomes.

Materials and methods

The Fracture Prevention Trial was a double-blind trial of postmenopausal women with osteoporosis and vertebral fractures randomly assigned to teriparatide (N = 541) or placebo (N = 544) administered by daily self-injection for a median of 19 months and a median follow-up of 21 months. All patients received calcium and vitamin D supplementation. Reports of nonvertebral fractures were collected from patients at each visit and confirmed by review of a radiograph or written radiology report. Nonvertebral fractures were recorded for the following sites: distal radius/wrist, humerus, rib/clavicle, hip, ankle, distal foot, pelvis, or other. Pathological fractures and fractures of the face, skull, metacarpals, fingers and toes were excluded. Fractures were classified by investigators as fragility or traumatic fractures. The three endpoints considered were six nonvertebral sites (nonvert-6), a set of common nonvertebral fractures described in a Food and Drug Administration Guidance document for the treatment and prevention of postmenopausal osteoporosis (FDA), and a European Union major set (major) of nonvertebral fractures.

Results

For teriparatide versus placebo, the point estimates for the RR of nonvert-6 (RR 0.54, P = 0.06; fragility RR 0.32, P = 0.014), FDA (RR 0.60, P = 0.15; fragility RR 0.38, P = 0.05), and major (RR 0.52, P = 0.02; fragility RR 0.38, P = 0.02) nonvertebral fracture endpoints were smaller than for the all nonvertebral fracture endpoint. Lower RRs were observed when the outcomes were limited to fragility fractures, and significant reductions in traumatic nonvertebral fractures were not observed.

Conclusion

In the Fracture Prevention Trial, the risk reduction for nonvertebral fracture in patients treated with teriparatide versus placebo depended on the set of nonvertebral fractures included in the analysis; lower RRs were observed for nonvertebral fractures most likely to be of osteoporotic origin. No significant reductions in traumatic nonvertebral fractures were observed.     

First fractures among postmenopausal women with osteoporosis

After the occurrence of the first fracture, osteoporosis is no longer a “silent” disease, and the patient’s risk for future fracture is increased several fold. We assessed the location of first osteoporotic fractures among women with osteoporosis. The Multiple Outcomes of Raloxifene Evaluation (MORE) trial was a fracture outcomes study of postmenopausal women with osteoporosis. All subjects received supplements containing 500 mg elemental calcium and 400–600 IU vitamin D. We assessed the location of first fractures among women with osteoporosis and no previous fractures at baseline from the placebo group of this trial after 3 years of follow-up. Prespecified fracture sites included vertebral fractures and nonvertebral fractures as defined in the MORE study protocol. Among 875 women (mean age, 64.5 ± 7.4 years) with no prevalent vertebral or nonvertebral fractures, 9% experienced their first fracture event during the trial. Fractures of radius and spine each occurred in 3% of patients. Fractures at other individual sites included ankle (0.6%), metatarsal (0.6%), humerus (0.5%), rib (0.5%), patella (0.3%), leg (0.2%), hip (0.2%), and clavicle (0.1%). These data suggest that for postmenopausal women with osteoporosis but no previous fractures, skeletal care should include a focus on preventing spine and radius fractures.     

Direct medical resource utilization associated with osteoporosis‐related nonvertebral fractures in postmenopausal women

The purposes of this study were to assess direct medical resource utilization related to the treatment of nonvertebral osteoporotic fractures within 1 year postfracture and to evaluate whether age impacts resource utilization. A previously‐validated algorithm for physician claims databases identified 15,327 women aged 50 years or older with incident fracture at nonvertebral osteoporotic sites between January 1, 2004 and December 31, 2005. Administrative databases of the health services available to all residents in Quebec served to study fracture‐related health resource utilization in the year after fracture. Data were linked by a unique personal identifier, creating a longitudinal cohort of all fracture cases for health resource utilization. The proportions of fractures treated by open reduction, closed reduction, immobilization or follow‐up by an orthopedic surgeon (OS) were evaluated. The mean number of claims for consultation with an OS or other clinicians in inpatient and outpatient visits, the hospitalization rate and length of stay (LOS) were assessed. Hip/femur fractures represented the highest rate of resource utilization because the majority of them required surgery (91.1%) and hospitalization (94.5%) with a mean (median) LOS of 39.2 (31) days. However, other nonvertebral fracture types needed significant clinical care related to surgery (27.9%), follow‐up consultation with an OS (77.6%), and hospitalization (27.3% of total LOS). Even pelvic fractures, which often do not require surgical treatment, commanded high resource utilization due to the high hospitalization rate (67.4%) with mean (median) LOS of 34.2 (26) days. Moreover, age was an important determinant of health resource utilization, being associated with an increased number of visits to other physicians, hospitalization, and length of hospitalization (LOS), admissions to long term care (LTC), and death. Osteoporosis‐related fractures accounted for substantial healthcare resource utilization. With an aging population and increased prevalence of fractures, strategies for osteoporosis management need to be introduced to reduce the healthcare burden. © 2013 American Society for Bone and Mineral Research     

Risk factors associated with incident clinical vertebral and nonvertebral fractures in postmenopausal women: the Canadian Multicentre Osteoporosis Study (CaMos)

Utilizing data from the Canadian Multicentre Osteoporosis Study (CaMos), we examined the association between potential risk factors and incident vertebral and nonvertebral fractures. A total of 5,143 postmenopausal women were enrolled. Information collected during the study included data from the CaMos baseline and annually mailed fracture questionnaires, the Short Form 36 (SF-36), the Health Utilities Index, and physical measurements. Participants were followed for 3 years. Postmenopausal women were classified into four groups according to their incident fracture status since baseline: those without a new fracture; those with a new clinically recognized vertebral fracture; those with an incident nonvertebral fracture at the wrist, hip, humerus, pelvis, or ribs (main nonvertebral fracture group); and those with any new nonvertebral fracture (any-nonvertebral-fracture group). We performed multivariate Cox proportional hazard analysis using all possible risk factors to determine the association between risk factors and the time to the first minimal trauma fracture. Best predictive models were also determined using variables that were included in the full models. The Bayesian information criterion was used for model selection. For all analyses, relative risks and associated 95% confidence intervals were calculated. During the follow-up period, 34, 163, and 280 women developed a vertebral, a main nonvertebral, or any nonvertebral fracture, respectively. The best predictive models indicated that a five point lower quality of life as measured by the SF-36 physical component summary score was associated with relative risks of 1.21 (95% CI, 1.02 to 1.44), 1.17 (95% CI, 1.07 to 1.28), and 1.19 (95% CI, 1.11 to 1.27) for incident vertebral, main nonvertebral, and all nonvertebral fractures, respectively. In addition, for a one standard deviation (SD=0.12) lower femoral neck BMD, the relative risks for incident vertebral, main nonvertebral, and any nonvertebral fractures increased by 2.73 (95% CI, 1.74 to 4.28), 1.39 (95% CI, 1.06 to 1.82), and 1.34 (95% CI, 1.09 to 1.65), respectively. Furthermore, various anthropometric measures, disease conditions, and medications are associated with a new fracture. Identifying postmenopausal women at risk is important given that fracture prevention therapies are now available.The authors wrote this article on behalf of the Camos Research Group.     

Multiple gene polymorphisms can improve prediction of nonvertebral fracture in postmenopausal women

Clinical risk factors (CRFs), with or without bone mineral density (BMD), are used to determine the risk of osteoporotic fracture (OF), which has a heritable component. In this study we investigated whether genetic profiling can additionally improve the ability to predict OF. Using 1229 unrelated Korean postmenopausal women, 39 single‐nucleotide polymorphisms (SNPs) in 30 human genomic loci were tested for association with osteoporosis‐related traits, such as BMD, osteoporosis, vertebral fracture (VF), nonvertebral fracture (NVF), and any fracture. To estimate the effects of genetic profiling, the genetic risk score (GRS) was calculated using five prediction models: (Model I) GRSs only; (Model II) BMD only; (Model III) CRFs only; (Model IV) CRFs and BMD; and (Model V) CRFs, BMD, and GRS. A total of 21 SNPs within 19 genes associated with one or more osteoporosis‐related traits and were included for GRS calculation. GRS associated with BMD before and after adjustment for CRFs (p ranging from <0.001 to 0.018). GRS associated with NVF before and after adjustment for CRFs and BMD (p ranging from 0.017 to 0.045), and with any fracture after adjustment for CRFs and femur neck BMD (p = 0.049). In terms of predicting NVF, the area under the receiver operating characteristic curve (AUC) for Model I was 0.55, which was lower than the AUCs of Models II (0.60), III (0.64), and IV (0.65). Adding GRS to Model IV (in Model V) increased the AUC to 0.67, and improved the accuracy of NVF classification by 11.5% (p = 0.014). In terms of predicting any fracture, the AUC of Model V (0.68) was similar to that of Model IV (0.68), and Model V did not significantly improve the accuracy of any fracture classification (p = 0.39). Thus, genetic profiling may enhance the accuracy of NVF predictions and help to delineate the intervention threshold. © 2013 American Society for Bone and Mineral Research.     

Different effects of antiresorptive therapies on vertebral and nonvertebral fractures in postmenopausal osteoporosis.

In postmenopausal osteoporosis, controlled clinical trials with antiresorptive therapies have shown consistent effects on vertebral fracture incidence while their effects on nonvertebral fractures, especially at the hip, have been reported with some agents, but not others. These discrepancies stress the differences in the pathogenesis of vertebral and nonvertebral fractures as discussed below, and the need to further investigate the mechanisms of action of various antiresorptive agents.     

Risk factors for urinary incontinence among postmenopausal Mexican women

Introduction and hypothesis

Previous studies of racial/ethnic variation in urinary incontinence (UI) suggest that population-specific studies of UI risk factors are needed to develop appropriate public health recommendations. We assessed UI risk factors among postmenopausal Mexican women enrolled in the Mexican Teachers’ Cohort.

Methods

We conducted a cross-sectional study among 15,296 postmenopausal women who completed the 2008 questionnaire. UI cases were women who reported experiencing UI during menopause. Self-reported potential UI risk factors included age, reproductive variables, smoking status, adiposity, and several health conditions. We estimated multivariate-adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) for UI using multivariable logistic regression.

Results

Among these postmenopausal women, the prevalence of UI was 14 %. Odds of UI were higher among women with ≥4 children vs nulliparous women (OR 1.43, 95 % CI 1.04–1.96) or body mass index (BMI) ≥30 vs <22 kg/m² (OR 2.00, 95 % CI: 1.55–2.57). Age at first birth <20 vs 20–24 years, past or current vs never smoking, larger waist-to-hip ratio, and history of asthma, high blood pressure, or diabetes were also associated with higher odds of UI (OR 1.2–1.3). We found a trend of lower odds of UI with older age.

Conclusions

Our data suggest that information about UI and UI prevention strategies might be particularly useful for Mexican postmenopausal women with 4 or more children or higher BMI. Further studies with longitudinal UI data, in addition to data on UI severity and subtype, are needed to provide more specific information about UI risk factors to Mexican women.

     

Risk factors for second hip fractures among elderly patients

Background  

Hip fractures following falls by the elderly, which increase with age, are increasing in number annually. The incidence of refracture (second hip fractures) has been reported to be 5%–10% in Japan and is expected to increase with the aging of the population in the future. Therefore, through a retrospective cohort study, we attempted to clarify the risk factors associated with second hip fractures.     

Obesity and fractures in postmenopausal women

Low body mass index (BMI) is a recognized risk factor for fragility fracture, whereas obesity is widely believed to be protective. As part of a clinical audit of guidance from the National Institute of Health and Clinical Excellence (NICE), we have documented the prevalence of obesity and morbid obesity in postmenopausal women younger than 75 years of age presenting to our Fracture Liaison Service (FLS). Between January 2006 and December 2007, 1005 postmenopausal women aged less than 75 years with a low‐trauma fracture were seen in the FLS. Of these women, 805 (80%) underwent assessment of bone mineral density (BMD) by dual energy X‐ray absorptiometry (DXA), and values for BMI were available in 799. The prevalence of obesity (BMI 30 to 34.9 kg/m²) and morbid obesity (BMI ≥ 35 kg/m²) in this cohort was 19.3% and 8.4%, respectively. Normal BMD was reported in 59.1% of obese and 73.1% of morbidly obese women, and only 11.7% and 4.5%, respectively, had osteoporosis (p < .0001). Multiple regression analysis revealed significant negative associations between hip T‐score and age (p < .0001) and significant positive associations with BMI (p < .0001) and previous fracture (p = .001). Our results demonstrate a surprisingly high prevalence of obesity in postmenopausal women presenting to the FLS with low‐trauma fracture. Most of these women had normal BMD, as measured by DXA. Our findings have important public heath implications in view of the rapidly rising increase in obesity in many populations and emphasize the need for further studies to establish the pathogenesis of fractures in obese individuals and to determine appropriate preventive strategies. © 2010 American Society for Bone and Mineral Research     

Independent predictors of all osteoporosis-related fractures among healthy Saudi postmenopausal women: the CEOR Study

This study was designed to identify independent predictors of all osteoporosis-related fractures (ORFs) among healthy Saudi postmenopausal women. We prospectively followed a cohort of 707 healthy postmenopausal women (mean age, 61.3±7.2 years) for 5.2±1.3 years. Data were collected on demographic characteristics, medical history, personal and family history of fractures, lifestyle factors, daily calcium intake, vitamin D supplementation, and physical activity score. Anthropometric parameters, total fractures (30.01 per 1000 women/year), special physical performance tests, bone turnover markers, hormone levels, and bone mineral density (BMD) measurements were performed. The final model consisted of seven independent predictors of ORFs: [lowest quartile (Q(1)) vs highest quartile (Q(4))] physical activity score (Q(1) vs Q(4): ≤12.61 vs ≥15.38); relative risk estimate [RR], 2.87; (95% confidence interval [CI]: 1.88-4.38); age≥60 years vs age<60 years (RR=2.43; 95% CI: 1.49-3.95); hand grip strength (Q(1) vs Q(4): ≤13.88 vs ≥17.28 kg) (RR=1.88; 95% CI: 1.15-3.05); BMD total hip (Q(1) vs Q(4): ≤0.784 vs 0.973 g/cm(2)) (RR=1.86; 95% CI: 1.26-2.75); dietary calcium intake (Q(1) vs Q(4): ≤391 vs ≥648 mg/day) (RR=1.66; 95% CI: 1.08-2.53); serum 25(OH)D (Q(1) vs Q(4): ≤17.9 vs ≥45.1 nmol/L) (RR=1.63; 95% CI: 1.06-2.51); and past year history of falls (RR=1.61; 95% CI: 1.06-2.48). Compared with having none (41.9% of women), having three or more clinical risk factors (4.8% of women) increased fracture risk by more than 4-fold, independent of BMD. Having three or more risk factors and being in the lowest tertile of T-score of [total hip/lumbar spine (L1-L4)] was associated with a 14.2-fold greater risk than having no risk factors and being in the highest T-score tertile. Several clinical risk factors were independently associated with all ORFs in healthy Saudi postmenopausal women. The combination of multiple clinical risk factors and low BMD is a very powerful indicator of fracture risk.     

Effectiveness of antiresorptives for the prevention of nonvertebral low-trauma fractures in a population-based cohort of women

Summary  Observational studies are needed to quantify real-life effectiveness of antiresorptive therapy in the prevention of clinical fractures. Antiresorptive therapies were associated with an overall 32% reduction in low-trauma nonvertebral fracture risk among women 50 and older. Effectiveness may be lower among older women and those without risk factors. Introduction  Randomized controlled trials have shown that antiresorptive therapies reduce the risk of fracture in selected populations, but further study is needed to quantify their real-life effectiveness. The study objective was to determine the association between antiresorptive use and low-trauma nonvertebral fracture in women 50 and older. Methods  The design was a retrospective nested case-control study (density-based sampling) within the Canadian Multicentre Osteoporosis Study. There were 5,979 eligible women with 453 cases and 1,304 matched controls. Results  The current use of antiresorptives was associated with a decreased risk of fracture with OR = 0.68, 95% CI: 0.52–0.91; where OR is the adjusted odds ratio and CI is the confidence interval. Subgroup analysis yielded OR = 0.61, 95% CI: 0.42–0.89 for ages 50–74; OR = 0.76, 95% CI: 0.50–1.17 for ages 75+; OR = 0.58, 95% CI: 0.40–0.83 for those with a major risk factor; and OR = 0.92; 95% CI: 0.59–1.42 for those without a major risk factor. Major risk factors were prevalent low-trauma fracture, vertebral deformity (grade 2+), and BMD T-score ≤ −2.5. Conclusions  Antiresorptive therapy is associated with a clinically important reduction in low-trauma nonvertebral fracture risk among community-dwelling women aged 50 and older. Antiresorptive therapy may be less effective for women 75 and older and women without major risk factors. See Acknowledgements for complete list of members of CaMos Research Group.     

Discriminatory ability of bone mass measurements (SPA and DEXA) for fractures in elderly postmenopausal women

Summary We investigated the discriminatory ability of forearm bone mineral content (BMC_arm) measured by single photon absorptiometry (SPA) and spinal bone mineral density (BMD_spine) measured by dual-energy X-ray absorptiometry (DEXA) in 387 elderly postmenopausal women. Of these, 22 had never sustained a fracture (normal), 91 had had less than three vertebral wedge fractures (mild), 51 had experienced a peripheral fracture (moderate), and 24 had had more than three vertebral wedge or compression fractures (severe). BMC_arm exceeded BMD_spine slightly in the ability to discriminate the mild and moderate groups (P< 0.01–0.001), whether calculations were performed on raw values or the Z-scores compared with premenopausal women. Receiver operating (ROC) analysis showed that at every cutoff level BMC_arm had a similar ability as BMD_spine to discriminate between the vertebral fracture (mild and severe) groups and healthy premenopausal and nonfractured postmenopausal women (normal), whereas BMC_arm had a significantly higher discriminatory ability of peripheral fractures (P< 0.05) (moderate) group compared with premenopausal women. We conclude that SPA and DEXA are equally capable as diagnostic procedures in women with established osteoporosis.     

Back problems among postmenopausal women taking estrogen replacement therapy: the study of osteoporotic fractures.

STUDY DESIGN: Cross-sectional and prospective. OBJECTIVES: To investigate the association between estrogen replacement therapy use, back pain, and back function in a large cohort of elderly women. BACKGROUND: Several studies have suggested that women who use estrogen replacement therapy may be more likely to experience back pain than those who do not. However, the relationships between estrogen replacement therapy, back pain, and impaired back function have not been clearly delineated. METHODS: At baseline information on estrogen replacement therapy use, functional status, back pain and function, and general lifestyle variables was obtained from 7209 elderly white women (mean age 71 years)enrolled in the Study of Osteoporotic Fractures. Lateral radiographs of the lumbar and thoracic spine were taken at baseline and at the third clinic visit, an average of 3.7 years after the baseline visit. Bone mineral density at the hip and spine was measured approximately 2 years after baseline. Follow-up information on back pain and function was also obtained at the third clinic visit. RESULTS: A total of 1039 (14.4%) women were using estrogen replacement therapy at baseline, 2016(28.0%) reported former use, and 4154 (57.6%) had never used estrogen replacement therapy. Compared with never-users, a statistically significant higher percentage of current estrogen users reported clinical back pain (52.7% vs. 43.4%) and back impairment (12.3% vs. 9.2%) at baseline and at the follow-up visit (pain 50.8% vs. 41%; impairment 16.0% vs. 12.1%). This occurred despite a higher prevalence of vertebral fractures in never-users of estrogen at the baseline visit. Current and former estrogen users without vertebral fractures had statistically significant higher likelihoods of having back pain and back dysfunction at both the baseline and third follow-up visit. The increased likelihood of back pain and back impairment in current and former estrogen users remained despite statistical adjustment for age, vertebral fracture, body mass index,smoking history, parity, exercise, arthritis, and diabetes in multivariate models. The relative risk (95%confidence interval) for impaired back function in former and current users at follow-up was 1.1 (0.9, 1.3) and 1.6 (1.3, 2.0), respectively. CONCLUSIONS: Our results indicate that postmenopausal estrogen use is associated with an increased likelihood of back pain and impaired back function in elderly white women.     

Weight loss and distal forearm fractures in postmenopausal women

Summary  

Weight loss is a risk factor for hip fractures, but few studies have evaluated the effect of weight loss on distal forearm fracture risk. In this longitudinal study including 7,871 postmenopausal women, weight loss of 5% or more was associated with an increased risk of distal forearm fractures.     

Prediction of incident osteoporotic fractures in elderly women using the free estradiol index

A decline in postmenopausal estrogen concentration accelerates postmenopausal bone loss. We have examined the predictive power of endogenous estrogen production, DXA hip bone density (BMD), and heel quantitative ultrasound (QUS) on incident clinical fracture in a prospective 3-year population based, randomised controlled trial of calcium supplementation. Baseline blood testing on 1499 women mean (SD) age 75 (3) years for estradiol and sex hormone binding globulin measurements and ankle QUS measurements (Lunar Achilles) was undertaken. Bone density was measured using DXA (Hologic 4500A) at 1 year. Incident clinical fractures were confirmed by X-ray. At 3 years, 10% had sustained more than one incident fracture. The fracture group had significantly lower levels of free estradiol index (FEI) (0.40±0.44 versus 0.49±0.54 pmol/nmol), hip BMD (0.776±0.129 versus 0.815±0.124 g/cm²) and measures of QUS (BUA 98±8 versus 101±8 db/Hz, SOS 1504±22 versus 1514 ±26 m/s; stiffness 67±11 versus 71±11 % mean young adult), respectively, than the non-fracture group. After adjustment for age, weight, use of topical estrogen, calcium supplementation and prevalent fracture, incident fracture was predicted by free estradiol index (HR per SD: 1.43:95%CI: 1.08–1.91, P=0.013). After adjustment for BMD, SOS or stiffness, the free estradiol index no longer predicted fracture. When examined separately, the presence of a vertebral or an appendicular fracture was associated with an 18% lower free estradiol index compared with no fracture. The risk of vertebral fracture increased with decreased free estradiol index (HR per SD reduction: 1.63:95% CI: 0.91–2.92); the risk of appendicular fracture also increased with decreased free estradiol index (HR per SD reduction: 1.45:95% CI: 1.05–2.01) after adjustment for age, weight, use of topical estrogen, calcium supplementation and prevalent fracture. After further adjustment for hip BMD or QUS measures, the effect of free estradiol index was no longer significant for vertebral or appendicular fractures. Therefore, a low free estradiol index increases the probability of having an incident fracture as a result of decreased BMD. These data confirm the importance of postmenopausal estrogen concentration in the pathogenesis of osteoporosis in elderly women.     

Vitamin D status and falls, frailty, and fractures among postmenopausal Japanese women living in Hawaii

Summary  

Vitamin D status and its relationship to physical performance, falls, and fractures in 495 postmenopausal women of Japanese ancestry in Hawaii were investigated. The mean 25-hydroxyvitamin D (25-OHD) was 31.94 ng/mL. No significant association of 25-OHD was demonstrated with most outcomes, possibly due to higher 25-OHD levels in this population.     

Does hormone-replacement therapy prevent fractures in early postmenopausal women?

The purpose of this population-based prospective cohort study was to examine the effect of hormone-replacement therapy (HRT) on the risk of fractures. The study population consisted of 7217 postmenopausal women aged 47-56 years (mean, 53.3 years) at baseline from data taken from the Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE) in Finland. We compared fracture incidences between HRT users and nonusers. A total of 679 (9.4%) women recorded validated fractures during the 5-year follow-up. Of these, 268 (39%) women had a distal forearm fracture. Two thousand six hundred seventy women (37%) had used HRT >6 months during the follow-up--one-half of them continuously. The relative risk, estimated as hazard ratio with Cox regression, was 0.69 (95% CI, 0.58-0.82) for any fracture and 0.49 (0.36-0.66) for distal forearm fracture among HRT users as compared with never-users. After adjusting for age, body mass index (BMI), number of chronic health disorders, fracture history, and time since menopause (independent risk factors) the corresponding risks were 0.67 (0.55-0.81) and 0.53 (0.37-0.74), respectively. The respective adjusted risks for continuous HRT users were 0.62 (0.48-0.79) and 0.41 (0.26-0.67). The adjusted risk of other than distal forearm fracture was 0.74 (0.55-0.98). The results suggest that HRT has a beneficial effect on prevention of fractures in general and on that of distal forearm fracture in particular in early postmenopausal women.