Risk Factors for Perimenopausal Distal Forearm Fracture

This prospective population-based cohort study investigated factors predicting distal forearm fracture (DFF) in perimenopausal women. The study population consisted of 11 798 women from the Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) Study in Finland. Mean baseline age of these women was 52.3 (SD 2.9) years (range 47–56 years) and 68% were postmenopausal. Three hundred and sixty-eight women (3.1%) had a validated DFF during the 5-year follow-up. Previous wrist fracture, postmenopausal state, age and nulliparity were independent predictors of DFF, while hormone replacement therapy (HRT), dairy calcium and overweight protected against it in multivariate Cox regression analysis: previous wrist fracture increased the DFF risk by 158% (p<0.0001), menopause by 69% (p= 0.002) and age by 6% per year (p= 0.010), whereas the continuous use of HRT decreased the risk by 63% (p= 0.0001), the use of dairy calcium at 1000–1499 mg/day (vs <500 mg/day) by 39% (p= 0.004), overweight (BMI >25 kg/m²) by 36% (p= 0.0002) and parity by 29% (p= 0.031). Combining dichotomous low weight, low use of calcium, non-use of HRT and previous wrist fracture into a risk score gave a dose–response effect by score level: the presence (vs absence) of all four risk factors resulted in a 12-fold DFF risk. Nevertheless, the sensitivity and specificity of the score for detecting DFF remained low. It was concluded that HRT, high nutritional calcium intake and overweight protect against but a history of wrist fracture predisposes to perimenopausal distal forearm fracture. A simple risk factor inquiry would help to identify perimenopausal women at high risk of distal forearm fracture. Received: 7 July 1999 / Accepted: 6 September 1999     

Risedronate Reduces the Risk of First Vertebral Fracture in Osteoporotic Women

Risedronate treatment reduces the risk of vertebral fracture in women with existing vertebral fractures, but its efficacy in prevention of the first vertebral fracture in women with osteoporosis but without vertebral fractures has not been determined. We examined the risk of first vertebral fracture in postmenopausal women who were enrolled in four placebo-controlled clinical trials of risedronate and who had low lumbar spine bone mineral density (BMD) (mean T-score =–3.3) and no vertebral fractures at baseline. Subjects received risedronate 5 mg (n= 328) or placebo (n= 312) daily for up to 3 years; all subjects were given calcium (1000 mg daily), as well as vitamin D supplementation (up to 500 IU daily) if baseline serum 25-hydroxyvitamin D levels were low. The incidence of first vertebral fracture was 9.4% in the women treated with placebo and 2.6% in those treated with risedronate 5 mg (risk reduction of 75%, 95% confidence interval 37% to 90%; P= 0.002). The number of patients who would need to be treated to prevent one new vertebral fracture is 15. When subjects were stratified by age, similar significant reductions were observed in patients with a mean age of 64 years (risk reduction of 70%, 95% CI 8% to 90%; P= 0.030) and in those with a mean age of 76 years (risk reduction of 80%, 95% CI 7% to 96%; P= 0.024). Risedronate treatment therefore significantly reduces the risk of first vertebral fracture in postmenopausal women with osteoporosis, with a similar magnitude of effect early and late after the menopause. Received: 12 September 2001 / Accepted: 11 December 2001     

Variation in the Efficacy of Hormone Replacement Therapy in the Prevention of Hip Fracture

Use of postmenopausal hormone replacement therapy (HRT) has been associated with a reduced risk of osteoporotic fractures. However, it is uncertain whether this risk reduction is modified by other risk factors for hip fracture. In a population-based case–control study in Sweden, we investigated the association between HRT and hip fracture risk within categories of age, body measures and lifestyle factors in postmenopausal women, 50–81 years of age. Mailed questionnaires and telephone interviews were used to collect data. Of those eligible, 1328 incident cases with hip fracture (82.5%) and 3312 randomly selected controls (81.6%) answered the questionnaire. Ever use of HRT in women less than 75 years old was associated with an odds ratio (OR) of 0.66 (95% confidence interval: 95% CI 0.50–0.87) for hip fracture compared with OR 0.40 (95% CI 0.21–0.77) in women 75 years or older. We found a significant interaction between HRT and both weight and physical activity (p<0.05). The protective effect of HRT was particularly pronounced in lean women: compared with never HRT users, ever users weighing under 60 kg had an OR of 0.44 (95% CI 0.30–0.66) whereas women weighing more than 70 kg had an OR of 0.91 (95% CI 0.53-1.-56). Women with low recent leisure physical activity (less than 1 h/week) similarly benefited more from HRT for hip fracture prevention than women with a higher degree of recreational physical activity. The observed interactions with weight and physical activity suggest that HRT has the best protective effect against hip fracture among high-risk women. Received: 7 October 1997 / Revised: 21 January 1998     

Association Between Colles’ Fracture and Low Bone Mass: Age-Based Differences in Postmenopausal Women

Colles’ fracture (CF) in postmenopausal women has been linked to low bone mass at the lumbar spine and hip. However, the diverse methodological approaches of previous studies make the results difficult to compare and thus the implications of CF in osteoporosis daily clinical practice are not clear. We explored the association between CF and low bone mineral density (BMD) in an incident case-control study in 58 postmenopausal Spanish women aged 45–80 years with recent CF and in 83 population-based controls of the same age range. The BMD of ultradistal distal forearm, lumbar spine and hip was measured by dual-energy X-ray absorptiometry (DXA) and WHO criteria were used to define osteoporosis and osteopenia. BMD was significantly lower in cases for all three areas (p<0.001). Osteoporosis was more prevalent in cases than controls in the wrist (60% vs. 35%, p<0.001), lumbar spine (47% vs. 20%, p<0.005) and hip (19% vs. 6%, p<0.005). After adjusting for age, menopausal status and body mass index, osteoporosis and osteopenia remained significantly associated with CF only in women aged 65 years or less (ultradistal forearm OR 5.7 (95% CI 1.2–27.2), lumbar spine OR 3.9 (95% CI 1.1–14.3)). We conclude that CF in postmenopausal women aged 65 or less may be used as a sentinel finding to identify patients with generalized osteoporosis. Additionally, 70% of all CF patients regardless of their age had low bone mass (T-score<−1SD) in any studied site. Received: 3 December 2001 / Accepted: 22 May 2002     

Physical Activity and Risk Factors for Hip Fractures in Thai Women

Hip fractures are among the most important causes of ill health and death among elderly people. Several potentially modifiable risk factors have been reported. Most claimed physical activity as a promising, inexpensive preventive measure for hip fracture. However, knowledge about risk factors for hip fracture in Asian populations is very limited. We therefore conducted a case–control study to assess the relationships between physical activity and risk of hip fractures in Thai women. From 14 hospitals in Thailand, 229 cases with a radiologically confirmed first hip fracture were enrolled. Two hundred and twenty-four controls were randomly recruited from the same neighborhood and were matched to the cases by age within a 5 year range. Information on physical activity as well as other potential confounders was obtained through personal interviews. Multivariate logistic regression revealed that past physical activity was protective in both very active and active women (OR = 0.67, 95% CI = 0.40–1.12 for moderately active women and OR = 0.20, 95% CI = 0.10–0.38 for very active women; p value for trend <0.01). Recent physical activity reduced the risk to about two-thirds (OR = 0.33, 95% CI = 0.19–0.60 and OR = 0.35, 95% CI = 0.18–0.69 for moderately and very active women respectively). In addition, breastfeeding was identified to be a protective factor (OR = 0.87, 95% CI = 0.80–0.94). In contrast, the following risk factors were identified: current use of antihistamine (OR = 13.96, 95% CI = 1.38–141.13) or traditional medicine (OR = 7.66, 95% CI = 2.71–21.63), underlying cerebrovascular diseases (OR = 6.53, 95% CI = 2.10–20.34), history of fracture (OR = 4.04, 95% CI = 1.26–12.99), parental Chinese racial background (OR = 2.52, 95% CI = 1.49–4.23), alcohol consumption (OR = 2.30, 95% CI = 1.04–5.09). Received: 14 April 2000 / Accepted: 17 October 2000     

Socioeconomic Status, Marital Status and Hip Fracture Risk: A Population-Based Case–Control Study

Socioeconomic status and social support have been identified as important determinants of several diseases and overall mortality, but these factors have not been adequately examined in relation to hip fracture risk. The aim of this study was to determine the relationship of socioeconomic status and marital status to hip fracture risk. We used data from a population-based case–control study in postmenopausal women aged 50–81 years during 1993–1995 who resided in six counties in Sweden. The analysis was based on 1327 incident cases of hip fracture and 3262 randomly selected controls. Socioeconomic and marital status were obtained by record linkage with census data in 1960, 1970, 1980 and 1990. Information on other possible risk factors for hip fracture was collected by a mailed questionnaire. Women who were gainfully employed in 1990 had an odds ratio (OR) of 0.74 [95% confidence interval (CI) 0.56–0.96] compared with those not gainfully employed; those in the highest tertile of household income had an OR of 0.74 (95% CI 0.60–0.90) compared with those in the lowest tertile of income. Women who lived in a one-family house had an OR of 0.85 (95% CI 0.72–0.99) compared with those living in an apartment. Divorced, widowed or unmarried women had a higher risk of hip fracture than married or cohabiting women; the OR was 1.40 (95% CI 1.06–1.85). Married women who were both gainfully employed and were living in a one-family house had a substantially decreased risk of hip fracture compared with unemployed women living without a partner in an apartment (OR 0.39; 95% CI 0.22–0.71). Occupational affiliation among women ever employed, and educational level, were not associated with hip fracture risk. We conclude that employment, household income, type of housing and marital status seem to be risk indicators of hip fracture risk independent of known osteoporotic risk factors. Received: 6 October 1999 / Accepted: 29 March 2000     

Prediction of Osteoporotic Fractures by Bone Densitometry and COLIA1 Genotyping: A Prospective, Population-Based Study in Men and Women

Osteoporosis is a common disease with a strong genetic component, characterized by reduced bone mineral density and increased fracture risk. Although the genetic basis of osteoporosis is incompletely understood, previous studies have identified a polymorphism affecting an Sp1 binding site in the COLIA1 gene that predicts bone mineral density and osteoporotic fractures in several populations. Here we investigated the role of COLIA1 genotyping and bone densitometry in the prediction of osteoporotic fractures in a prospective, population-based study of men (n= 156) and women (n= 185) who were followed up for a mean (± SEM) of 4.88 ± 0.03 years. There was no significant difference in bone density, rate of bone loss, body weight, height, or years since menopause between the genotype groups but women with the “ss” genotype were significantly older than the other genotype groups (p= 0.03). Thirty-nine individuals sustained 54 fractures during follow-up and these predominantly occurred in women (45 fractures in 30 individuals). Fractures were significantly more common in females who carried the COLIA1“s” allele (p= 0.001), although there was no significant association between COLIA1 genotype and the occurrence of fractures in men. Logistic regression analysis showed that carriage of the COLIA1“s” allele was an independent predictor of fracture in women with an odds ratio (OR) [95% CI] of 2.59 [1.23–5.45], along with spine bone mineral density (OR = 1.57 [1.04–2.37] per Z-score unit) and body weight (OR = 1.05 [1.01–1.10] per kilogram). Moreover, bone densitometry and COLIA1 genotyping interacted significantly to enhance fracture prediction in women (p= 0.01), such that the incidence of fractures was 45 times higher in those with low BMD who carried the “s” allele (24.3 fractures/100 patient-years) compared with those with high BMD who were “SS” homozygotes (0.54 fracture/100 patient-years). We conclude that in our population, COLIA1 genotyping predicts fractures independently of bone mass and interacts with bone densitometry to help identify women who are at high and low risk of sustaining osteoporotic fractures. Received: 16 November 2000 / Accepted: 9 June 2000     

Risk Factors for Perimenopausal Fractures: A Prospective Study

This prospective study was aimed at determining the risk factors for the development of fractures in perimenopausal women. The study group (n= 3068) was comprised of a stratified population sample of women aged between 47 and 56 years. During the follow-up period of 3.6 years, 257 (8.4%) of the women sustained a total of 295 fractures. After adjustment for covariates, the relative risk (RR) of sustaining a fracture was found to be 1.4 [95% confidence interval (CI) 1.2–1.6] for a 1 standard deviation (SD) decrease in the spinal and femoral neck bone mineral density (BMD). Women with a previous fracture history were found to have an increased risk of fracture [RR 1.7 (95% CI 1.3–2.2)] and those reporting three or more chronic illnesses exhibited a RR of 1.4 (95% CI 1.0–1.9). Women not using hormone replacement therapy (HRT) had a RR of 1.5 (95% CI 1.1–2.2) for all fracture types. When osteoporotic fractures (vertebral, hip, proximal humerus and wrist fractures; n= 98) were used as an endpoint, the independent risk factors were found to be a low BMD (RR for a 1 SD decrease in both spinal and femoral neck BMD was 1.6, 95% CI 1.3–2.0), a previous fracture history (RR 1.9, 95% CI 1.3–2.9) and nonuse of HRT (RR 2.2, 95% CI 1.3–4.0). The independent risk factors for all other fractures (n = 158) were a low BMD (RR for a 1 SD decrease in the spinal BMD was 1.4, 95% CI 1.2–1.6 and in the femoral neck BMD was 1.3, 95% CI 1.1–1.5), a previous fracture history (RR 1.6, 95% CI 1.1–2.2), smoking (RR 1.8, 95% CI 1.1–2.7) and having had three or more chronic illnesses (RR 1.6, 95% CI 1.1–2.2). Weight, height, age, menopausal status, maternal hip fracture, use of alcohol, coffee consumption or dietary calcium intake were not independently associated with the development of any particular type of fracture. We conclude that the independent risk factors for perimenopausal fractures are a low bone density, previous fracture history, nonuse of HRT, having had three or more chronic illnesses and smoking, the gradient of risk being similar for spinal and femoral neck BMD measurements in the perimenopausal population. The risk factors are slightly different for perimenopausal osteoporotic than for other types of fractures. Received: 6 April 1999 / Accepted: 18 August 1999     

Questionnaire about Calcium Intake: Can We Trust the Answers?

The aim of this study was to construct and evaluate reliable questions concerning calcium intake and to include them in a questionnaire to be used in a community-based intervention program for preventing osteoporosis. Estimating calcium intake is an important factor in evaluating risk profiles for community residents. A very large amount of calcium in the Swedish diet comes from dairy foods. Two questionnaires were designed. Questionnaire A contained eight questions concerning consumption of dairy foods. Questionnaire B contained 52 questions on consumption of calcium-rich food groups and dishes, and also included the eight questions mentioned above. Questionnaire A was sent to 467 randomized women aged 20–30 and 50–60 years. Women with a low calcium intake also answered questionnaire B. In order to validate the questionnaires a selected number of the women were interviewed using a dietary history. In total 363 women answered questionnaire A, 118 of whom had a calcium intake below the recommended amount. Ninety-six women completed questionnaire B. Twenty-two women were interviewed with the dietary history. Statistical analyses using t-tests of the differences between answers to the same questions in two questionnaires and the interview, gave the following results. Questionnaire A provides reliable information about those who do not reach the recommended level of calcium intake. Questionnaire B does not provide any more information than questionnaire A. It is not possible to rank calcium levels in the diet with the questionnaires. Using the estimated calcium intake from dairy foods obtained in questionnaire A, individuals at risk of consuming less than the recommended intake of calcium can be identified, as can those consuming the required amount. In conclusion, questionnaire A is useful in discriminating between subjects with low and high calcium intake. Received: 12 December 1997 / Accepted: 3 July 1998     

Fractures Before Menopause: A Red Flag for Physicians

There is substantial interest in the early identification of women at risk for osteoporotic fractures, so that preventive measures may be instituted early. We examined whether women with a history of fractures before menopause were at an increased risk of fractures after menopause. We obtained information about any lifetime fractures of the hip, arm, spine, wrist, leg, ankle, foot and finger from 9086 ambulatory white women ages 65 years and older participating in the Study of Osteoporotic Fractures. We also measured bone mineral density and recorded history of falls, maternal fracture history, drug use, diet, functional status, and other characteristics commonly associated with osteoporotic fractures. We used proportional hazards models to estimate the effects of fractures that occurred before menopause on the risk of fractures after menopause, in particular those that occurred during the 12 years of study follow-up. The risk of fractures of all types during the study period was greater among women with a premenopausal fracture of any type compared with women without a premenopausal fracture (hazard ratio (HR), 1.33; 95% confidence interval (CI), 1.14–1.56; p<0.001). Adjustment for possible confounders, including bone mineral density, had only a modest effect (HR, 1.25; 95% CI, 1.03–1.50; p<0.02). An increased risk of fracture among women with a premenopausal fracture was also seen after stratification by estrogen use, propensity to fall and maternal fracture history. Premenopausal fractures are therefore a risk factor for subsequent fractures independent of other risk factors for osteoporotic fractures, such as bone mineral density. A fracture history, including fractures before menopause, should be obtained when making decisions about preventive treatments. Received: 17 April 2000 / Accepted: 14 June 2000     

Prevalence of Osteoporosis by Educational Level in a Cohort of Postmenopausal Women

To evaluate whether the prevalence of osteoporosis and related risk factors might be influenced by the level of education, as has been demonstrated for many other chronic diseases, 6160 postmenopausal women at their first densitometric referral were interviewed about reproductive variables, past and current use of estrogens, prevalence of chronic diseases, and lifestyle factors such as calcium intake, physical activity, smoking and overweight. This sample was stratified by years of formal education. Densitometric evaluation was performed by dual-energy X-ray absorptiometry. Age at menarche, past exposure to oral contraceptives, use of hormone replacement therapy, prevalence of chronic diseases, physical activity, overweight and smoking showed significant trends according to the years of education. The prevalence of osteoporosis showed an inverse relationship with level of education, ranging from 18.3% for the most educated to 27.8% for the least educated women. Multiple logistic regression analysis demonstrated a predictive role toward osteoporosis by age, age at menarche and menopause, hormone replacement therapy, calcium intake, physical activity and body mass index. Using the lowest educational level as reference category, increases in educational status were associated with a significantly reduced risk for osteoporosis (OR = 0.76, 95% CI 0.65–0.90 for 6–8 years of schooling; OR = 0.68, 95% CI 0.57–0.82 for 9 years or more). This study shows differences in the prevalence of osteoporosis among educational classes and the protective role played by increases in formal education. If these results are confirmed in other population studies, public health intervention programs will have to consider the socioeconomic and cultural background of the population strata that run a greater risk of osteoporosis. Received: 7 March 1998 / Accepted: 9 July 1998     

Multisite Quantitative Ultrasound: Colles’ Fracture Discrimination in Postmenopausal Women

Distal forearm fractures are the most common perimenopausal fracture and are generally associated with osteoporosis. The aim of this study was to evaluate the capability of speed of sound (SOS) measurements in cortical bone at the phalanx, radius, tibia and metatarsal to discriminate Colles’ fracture cases from controls in postmenopausal women and to compare this with bone mineral density (BMD) measurements obtained by dual-energy X-ray absorptiometry (DXA). Sixty-three postmenpausal Colles’ fracture cases and 191 postmenopausal controls had SOS measurements of the radius, tibia, phalanx and metatarsal using a semi-reflection ultrasound technique and BMD measurements of the lumbar spine and proximal femur using DXA. The age-adjusted odds ratios (ORs) for fracture for the SOS measurement sites were 1.50 [95% CI 1.07–2.10] for the radius, 1.23 [0.86-1.76] for the tibia, 1.85 [1.06–3.23] for the phalanx and 1.74 [1.12–2.71] for the metatarsal site. For the BMD measurements the ORs were 1.95 [1.34–2.85] for the lumbar spine, 2.21 [1.43–3.40] for the femoral neck and 2.62 [1.69–4.08] for the total hip. The benefits of combining sites either by taking their average Z-score or by using the manufacturer’s ORI algorithm were evaluated. The two methods yielded similar results and the ORs for the combination of the radius and phalanx were 2.00 [1.21–3.33], for the radius and metatarsal 1.67 [1.05–2.67], for the phalanx and metatarsal 1.86 [1.11–3.08] and for the radius, phalanx and metatarsal 1.81 [1.07–3.06]. Combinations of DXA sites gave 2.22 [1.44–3.41] for the lumbar spine and femoral neck and 2.41 [1.57–3.70] for the lumbar spine and total hip. In conclusion, semi-reflection ultrasound measurements at the radius, phalanx or metatarsal demonstrated an ability to discriminate fracture cases from controls in postmenopausal Colles’ fracture patients, although the odds ratios were lower than with spine and femur BMD. Received: 6 July 2001 / Accepted: 11 December 2001     

Differences in Risk Factor Patterns Between Cervical and Trochanteric Hip Fractures

The two types of hip fracture – cervical and trochanteric femoral fractures – are generally considered together in etiologic studies. However, women with a trochanteric fracture may be more osteoporotic than those with cervical hip fractures, and have higher post-fracture mortality. To explore differences in risk factor patterns between the two types of hip fracture we used data from a large population-based case–control study in Swedish women, 50–81 years of age. Data were collected by questionnaire, to which more than 80% of subjects responded. Of the cases included, 811 had had a cervical fracture and 483 a trochanteric fracture during the study period; these cases were compared with 3312 randomly selected controls. Height and hormonal factors appeared to affect the risk of the two types of hip fracture differently. For every 5 cm of current height, women with a cervical fracture had an adjusted odds ratio (OR) of 1.23 (95% CI 1.15–1.32) compared with an OR of 1.06 (95% CI 0.97–1.15) for women with trochanteric fractures. Later menopausal age was protective for trochanteric fractures (OR 0.95, 95% CI 0.91–0.99 per 2 years) but no such association was found for cervical fractures. Compared with never smokers, current smokers had an OR of 1.48 (95% CI 1.12–1.95) for trochanteric fractures and 1.22 (95% CI 0.98–1.52) for cervical fractures. Current hormone replacement therapy was similarly protective for both fracture types, but former use substantially reduced risk only for trochanteric fractures: OR 0.55 (95% CI 0.33–0.92) compared with 1.00 (95% CI 0.71–1.39) for cervical fractures. These risk factor patterns suggest etiologic differences between the fracture types which have to be considered when planning preventive interventions. Received: 22 March 1999 / Accepted: 28 May 1999     

Bone Mineral Densitometry Substantially Influences Health-Related Behaviors of Postmenopausal Women

Although bone mineral density measurements are helpful in predicting future risk for osteoporotic fractures, there is limited information available on how the results of bone densitometry influence a woman's use of therapeutic alternatives. To assess the role of bone mineral densitometry in influencing postmenopausal women to change health behaviors associated with osteoporosis, we prospectively followed, for an average of 2.9 years, 701 postmenopausal women over 50 years of age referred to an osteoporosis prevention program in a large metropolitan area. Assessments included bone mineral densitometry by dual-energy X-ray absorptiometry (with classification of skeletal health), medical history, use of hormone replacement therapy, calcium intake, caffeine intake, exercise, smoking habits, and fall precaution measures. Women classified at baseline with moderate low bone mass were twice as likely (33%), and women with severe low bone mass more than three times as likely (47%) to start hormone replacement therapy compared with women with a normal result (13%, P < 0.001). This was true regardless of whether they had taken hormone replacement therapy in the past. Below-normal BMD was a strong predictor of a woman's initiation of hormone replacement therapy (OR 4.2; 95% CI 2.7–6.4; P < 0.05) even after adjustment for age, education, history of osteoporosis or fracture, and medical condition related to osteoporosis. Women with moderate or severe low bone mass were also much more likely to start calcium supplements (81–90% versus 67%), increase dietary calcium (71–82% versus 60%), decrease use of caffeine (44–60% versus 34%), start exercising (61–76% versus 52%), and quit smoking (22–24% versus 11%) relative to their behaviors prior to testing (P < 0.01). In conclusion, postmenopausal women report that the results of bone densitometry substantially influence the decision to begin hormone replacement therapy and calcium supplements, increase dietary calcium, decrease caffeine, increase exercise, decrease smoking, and take precautions to prevent falls. More studies are needed to measure the long-term effects of this influence. Received: 19 March 1999 / Accepted: 13 August 1999     

Proximal Femur Geometry To Detect and Distinguish Femoral Neck Fractures from Trochanteric Fractures in Postmenopausal Women

Some proximal femur geometry (PFG) parameters, measured by dual-energy X-ray absorptiometry (DXA), have been reported to discriminate subjects with hip fracture. Relatively few studies have tested their ability to discriminate femoral neck fractures from those of the trochanter. To this end we performed a cross-sectional study in a population of 547 menopausal women over 69 years of age with femoral neck fractures (n= 88), trochanteric fractures (n= 93) or controls (n= 366). Hip axis length (HAL), neck–shaft angle (NSA), femoral neck diameter (FND) and femoral shaft diameter (FSD) were measured by DXA, as well as the bone mineral density (BMD) of the nonfractured hip at the femoral neck, trochanter and Ward’s triangle. In fractured subjects, BMD was lower at each measurement site. HAL was longer and NSA wider in those with femoral neck fractures. With logistic regression the age-adjusted odds ratio (OR) for a 1 standard deviation (SD) decrease in BMD was significantly associated at each measurement site with femoral neck fracture (femoral neck BMD: OR 1.9, 95% confidence interval (95% CI): 1.4–2.5; trochanter BMD: OR 1.6, 95% CI 1.2–2.0; Ward’s triangle BMD: OR 1.7, 95% CI 1.3–2.2) and trochanteric fracture (femoral neck BMD: OR 2.6, 95% CI 1.9–3.6; trochanter BMD: OR 3.0, 95% CI 2.2–4.1; Ward’s triangle BMD: OR 1.8, 95% CI 1.4–2.3). Age-adjusted OR for 1 SD increases in NSA (OR 2.2, 95% CI 1.7–2.8) and HAL (OR 1.3, 95% CI 1.1–1.6) was significantly associated with the fracture risk only for femoral neck fracture. In the best predictive model the strongest predictors were site-matched BMD for both fracture types and NSA for neck fracture. Trochanteric BMD had the greatest area (0.78, standard error (SE) 0.02) under the receiver operating characteristic curve in trochanteric fractures, whereas for NSA (0.72, SE 0.03) this area was greatest in femoral neck fractures. These results confirm the association of BMD with proximal femur fracture and support the evidence that PFG plays a significant role only in neck fracture prediction, since NSA is the best predictive parameter among those tested. Received: 24 April 2001 / Accepted: 1 August 2001     

Characteristics of Falls and Risk of Hip Fracture in Elderly Men

The steep rise in hip fracture incidence rates with age is not fully explained by an increase in the frequency of falls or by reduction in bone mineral density, suggesting that circumstances of falls may also affect the risk of hip fracture. Previous studies conducted mainly among women have identified the importance of the orientation of a fall in the etiology of hip fracture. In this case–control study among men of 45 years and older, we evaluated how the circumstances of falls affect the risk of hip fracture. We compared 214 cases with hip fracture due to a fall with 86 controls who had fallen within the past year but did not sustain a hip fracture. As expected, in multivariable age-adjusted analyses men who reported hitting the hip/thigh in a fall had a markedly elevated risk of hip fracture (OR = 97.8; 95% CI = 31.7–302). Hitting the knee in a fall was associated with reduced risk (OR = 0.24; 95% CI = 0.09–0.67). Other factors that were associated with reduced risk of hip fracture among men who fell were more hours of physical activity in the past year (OR = 0.84; 95% CI = 0.73–0.97, for each additional 4 h per week), a greater body mass index (OR = 0.60; 95% CI = 0.40–0.90, for each additional 4 kg/m²), and a history of a fracture when age 45 years or older (OR = 0.26; 95% CI = 0.10–0.69). Reported lower limb dysfunction was associated with increased risk of hip fracture (OR = 6.41; 95% CI = 2.09–19.6) among fallers. The increased risk associated with hitting the hip/thigh in a fall and the reduced risk associated with high body mass index suggest that preventive efforts for older men at high risk might include protective hip pads to reduce the force on the hip in a fall. Exercise and strength training programs may also reduce the risk of hip fracture among men who fall. Received: 12 May 1997 / Accepted: 14 October 1997     

The Injury Mechanisms of Osteoporotic Upper Extremity Fractures Among Older Adults: A Controlled Study of 287 Consecutive Patients and Their 108 Controls

The risk factors for falls in older adults are well known but knowledge on the direct injury mechanisms that result in various osteoporotic fractures has been very sparse. The purpose of this study was therefore to clarify the injury mechanisms of osteoporotic upper extremity fractures of older adults and to compare these mechanisms with those of the control fallers, and in this way to obtain reliable insight into the etiology and pathogenesis of upper extremity fractures and thus to enable fracture prevention. One hundred and twelve patients with a fresh fracture of the proximal humerus, 65 patients with an elbow fracture, 110 patients with a wrist fracture and 108 controls (no fracture, or a fracture other than the case fracture) were interviewed and examined between September 1995 and December 1997. The inclusion criteria of the subjects were that the patient was 50 years of age or older at the time of the accident, and that the fracture/injury had occurred as a result of low-energy trauma (typically a fall from standing height or less) within a week before the interview and examination. In 97% of patients with a proximal humerus or elbow fracture, and in all patients (100%) with a wrist fracture, the fracture was a result of a fall. In the control group this figure was 93%. In a polychotomous logistic regression analysis the intergroup differences in the fall directions (adjusted by gender, age and functional capacity) were statistically highly significant (χ²= 43.6, d.f. = 15, p<0.001). Most of the patients with a proximal humerus fracture or elbow fracture reported that they had fallen “obliquely forward” (43% and 38%) or “to the side” (29% and 26%), whereas in the wrist fracture group the main fall direction was also “obliquely forward” (34%) but the other fall directions (i.e., “forward”, “to the side”, “obliquely backward” and “backward”) were quite equally represented (13–19%). The odds ratio (OR) for an obliquely forward fall resulting in a proximal humerus fracture was 3.5 [95% confidence interval (CI) 1.4–9.2), as compared with the fall directions of the controls and the “obliquely backward” fall direction. In a logistic regression analysis the patients with a wrist fracture managed to break their fall (e.g., with an outstretched arm) more frequently than the patients in the other groups (OR 3.9; 95% CI 2.0–7.3). The patients with a proximal humerus fracture, in turn, managed to break their fall less frequently than the controls (OR 0.33; 95% CI 0.14–0.80). The same was true of the patients with an elbow fracture, although the difference was not significant (OR 0.49%; 95% CI 0.19–1.3). As objective evidence for a direct fall-induced impact on the fracture site, 68% of patients with a proximal humerus fracture revealed a fresh subcutaneous hematoma on the shoulder/upper arm, while such a hematoma was rare in the controls (2%) (p<0.001). Correspondingly, 62% of patients with an elbow fracture showed a similar hematoma on the elbow area, while this was seen in none of the controls (p<0.001). In patients with a wrist fracture a hand/wrist hematoma was seen in 58% of the victims, as compared with 18% of the controls (p<0.001). The study shows that the most typical osteoporotic upper extremity fractures of older adults have their specific injury mechanisms. A great majority of these fractures occur as a result of a fall and a subsequent direct impact of the fractured site. Effective fracture prevention could be achieved by minimizing the obvious risk factors of falling and reducing the fall-induced impact force with injury site protection. Received: 13 January 2000 / Accepted: 11 April 2000     

Combined Calcium and Vitamin D3 Supplementation in Elderly Women: Confirmation of Reversal of Secondary Hyperparathyroidism and Hip Fracture Risk: The Decalyos II Study

Vitamin D insufficiency and low calcium intake contribute to increase parathyroid function and bone fragility in elderly people. Calcium and vitamin D supplements can reverse secondary hyperparathyroidism thus preventing hip fractures, as proved by Decalyos I. Decalyos II is a 2-year, multicenter, randomized, double-masked, placebo-controlled confirmatory study. The intention-to-treat population consisted of 583 ambulatory institutionalized women (mean age 85.2 years, SD = 7.1) randomized to the calcium–vitamin D₃ fixed combination group (n= 199); the calcium plus vitamin D₃ separate combination group (n= 190) and the placebo group (n= 194). Fixed and separate combination groups received the same daily amount of calcium (1200 mg) and vitamin D₃ (800 IU), which had similar pharmacodynamic effects. Both types of calcium-vitamin D₃ regimens increased serum 25-hydroxyvitamin D and decreased serum intact parathyroid hormone to a similar extent, with levels returning within the normal range after 6 months. In a subgroup of 114 patients, femoral neck bone mineral density (BMD) decreased in the placebo group (mean =–2.36% per year, SD = 4.92), while remaining unchanged in women treated with calcium-vitamin D₃ (mean = 0.29% per year, SD = 8.63). The difference between the two groups was 2.65% (95% CI =–0.44, 5.75%) with a trend in favor of the active treatment group. No significant difference between groups was found for changes in distal radius BMD and quantitative ultrasonic parameters at the os calcis. The relative risk (RR) of HF in the placebo group compared with the active treatment group was 1.69 (95% CI = 0.96, 3.0), which is similar to that found in Decalyos I (RR = 1.7; 95% CI = 1.0, 2.8). Thus, these data are in agreement with those of Decalyos I and indicate that calcium and vitamin D₃ in combination reverse senile secondary hyperparathyroidism and reduce both hip bone loss and the risk of hip fracture in elderly institutionalized women. Received: 23 March 2001 / Accepted: 28 October 2001     

Effect of Soy Protein on Bone Metabolism in Postmenopausal Japanese Women

We conducted a cross-sectional study of the effects of soybean protein intake on bone mineral density and biochemical markers in 85 postmenopausal Japanese women. Nutrients in the diet of postmenopausal Japanese women visiting the osteoporosis unit, including subjects with normal lumbar spine bone mineral density (L2–4 BMD), were investigated by questionnaire, and the calculated daily energy, protein, soy protein and calcium intake were obtained. L2–4 BMD was measured with dual-energy X-ray absorptiometry, and assays done of serum alkaline phosphatase (ALP) and serum intact osteocalcin (IOC) as bone formation markers and urinary pyridinoline (UPYR) and urinary deoxypyridinoline (UDPYR) as bone resorption markers. Soy protein intake was significantly associated with the Z-score for L2–4 BMD (r= 0.23, p = 0.038) and UDPYR (r =−0.23, p = 0.034). Stepwise multiple regression analyses showed that soy protein intake is significantly associated with the Z-score for L2–4 BMD (β= 0.225, p = 0.04) and UDPYR (β=−0.08, p = 0.03) among four nutritional factors. These results suggest that high soy protein intake is associated with a higher bone mineral density and a lower level of bone resorption, but further studies are needed to confirm the causal dynamic mechanisms. Received: 17 September 1999 / Accepted: 29 February 2000     

Performance of COLIA1 Polymorphism and Bone Turnover Markers to Identify Postmenopausal Women with Prevalent Vertebral Fractures

Some studies have suggested that bone turnover markers (BTM) and collagen type I alpha 1 gene (COLIA1) may be useful in the prediction of rates of future bone loss, and may therefore provide information about fracture risk. Our study aimed to examine the association of the COLIA1 genotype with the risk of vertebral fracture and to investigate the predictive value of this genetic factor in comparison with bone mineral density (BMD) and BTM, in ambulatory postmenopausal Spanish women. We determined the COLIA1 polymorphism by polymerase chain reaction, BMD by dual-energy X-ray absorptiometry and BTM in 43 postmenopausal women with prevalent vertebral fracture and a control group of 101 postmenopausal women without fracture. There was a significant overrepresentation of the ‘T’ allele in fractured women (p= 0.029). BTM exhibited no differences between women with or without fractures or COLIA1 genotype groups. After adjusting for all other variables, the osteoporosis densitometric criteria variable was the most strongly associated with fracture (OR = 5 [1.8–13.3]) followed by COLIA1 (OR = 2.1 [1–4.3] per copy of the ‘T’ allele). Our study shows that COLIA1 is associated with prevalent vertebral fracture independently of bone mass, and the performance of this genetic factor to assess prevalent vertebral fracture is better than bone turnover markers. Received: 29 June 2001 / Accepted: 11 December 2001