Marjo Tuppurainen

Bone Mineral Density and Risk Factors For Osteoporosis--A Population-Based Study of 1600 Perimenopausal Women

Population-based epidemiological studies on osteoporosis are few. Our study evaluated the effects of menopause and certain putative behavioral risk factors on bone mineral density (BMD). Spinal and femoral neck BMD were measured with dual X-ray absorptiometry (DXA) from 1600 perimenopausal women aged 48–59 years (mean 53.2 years) with no diseases or medications known to affect bone metabolism. These women were a selected sample of the Kuopio Osteoporosis Risk Factor and Prevention Study population (n=14,220). There was a wide variation of BMD among perimenopausal women. Menopause had a major effect on BMD. Postmenopausal women had significantly lower BMD in both spine (-6.2%) and femoral neck (-3.9%) as compared with premenopausal women. Multiple regression analysis showed that weight, menopausal status, age, and grip strength were significant independent predictors of both spinal and femoral BMD. Additionally, physical activity was found to be a significant predictor of femoral BMD, and alcohol consumption was a significant predictor of spinal BMD. However, current anthropometric and lifestyle factors explained only 18.7–25.4% of the variability of BMD. Therefore, the estimation of the risk factor status at menopause is not an adequate substitute for bone densitometry. However, our results may in part help clinicians to identify the risk groups at which to direct bone density measurements.

HRT and Vit D in prevention of non-vertebral fractures in postmenopausal women; a 5 year randomized trial

OBJECTIVES We investigated the incidence of new non-vertebral fractures during HRT or low-dose vitamin (Vit) D3 supplementation in a 5-year prospective trial. METHODS A total of 464 early postmenopausal women, (a subgroup of the Kuopio Osteoporosis Study, n = 13100) were randomized to four groups: (1) HRT, a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate; (2) Vit D (300 IU/day and 100 IU/day during the fifth year); (3) HRT + Vit D; and (4) placebo. Lumbar (L2-4) and femoral neck bone mineral densities (BMD) were determined by dual X-ray absorptiometry (DXA) at baseline, after 2.5 and 5 years of treatment. All new symptomatic non-vertebral, radiographically defined fractures were recorded. RESULTS Altogether, 368 women (79%) completed the 5 year treatment. In all, 32 women had 39 non-vertebral fractures during a mean of 4.3 year follow-up (HRT 4, Vit D 10, HRT + Vit D 8 and placebo 17). The reduction in the incidence of new non-verterbral fractures was significant in women with HRT alone (P = 0.032) when adjusted by baseline BMD and previous fractures; observed also with the intention-to-treat principle (P = 0.048). When the HRT groups were pooled, HRT showed a significantly lower incidence of new non-vertebral fractures (P = 0.042) than women receiving placebo and also after adjusting as above (P = 0.016); both in valid-case and in the intention-to-treat analysis. In the Vit D group, the fracture incidence was non-significantly decreased (P = 0.229) in comparison with the placebo group. The estimated risk of new non-vertebral fractures among women treated with HRT alone was 0.29 (95% CI, 0.10-0.90) and with Vit D 0.47 (95% CI, 0.20-1.14) and with HRT + Vit D 0.44 (95% CI, 0.17-1.15), in comparison with the placebo group (adjusted by femoral BMD and previous fractures). CONCLUSIONS This study is the first prospective trial confirming the beneficial effect of HRT on prevention of peripheral fractures in non-osteoporotic postmenopausal women. The effect of low-dose Vit D remains to be proved.

The effect of gynecological risk factors on lumbar and femoral bone mineral density in peri- and postmenopausal women

The relationship between gynecological history and bone mineral density (BMD) of the lumbar spine and femoral neck was studied in 3126 perimenopausal women. The study population was a random, stratified sample of participants, selected from the Kuopio Osteoporosis Study, which consisted primarily of all 14,220 women aged 47-56 years in Kuopio Province in 1989. After exclusion of 1521 women reporting past or present hormonal replacement therapy (HRT), 1605 women formed the final study population. Present HRT users had significantly higher lumbar BMD but not femoral BMD, than non-hormone users. Postmenopausal status, late menarche, and bilateral oophorectomy were risk factors for low BMD. Protective factors against low BMD were increased body weight, increased number of pregnancies, as well as hysterectomy without bilateral oophorectomy. The majority (43.8%) of these operations had been performed due to the presence of leiomyomas. No significant correlation was found between nulliparity, breast-feeding or amenorrhea before the age of 30 and BMD. In the multiple regression analysis, gynecological variables could account for only 18.4-26.8% of the variance in BMD, while time since last periods, age, age at menarche, weight and hysterectomy were the most significant variables. We conclude that reproductive history gives rise to some special risk groups, to whom BMD measurements and osteoporosis prevention efforts should be directed. However, it is impossible to predict BMD by gynecological characteristics.

Use of calcium supplements and the risk of coronary heart disease in 52-62-year-old women: The Kuopio Osteoporosis Risk Factor and Prevention Study.

BACKGROUND To analyse prospectively the effect of calcium or calcium+D supplementation on coronary heart disease (CHD) in 52-62-year-old women. METHODS AND RESULTS 10,555 52-62-year-old women from the population-based Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE) who did not have CHD at baseline were followed for nearly 7 years in 1994-2001. Information about use of calcium supplements and health events was obtained from two repeated questionnaires in 1989 and 1994. Information about causes of death during the follow-up was obtained from the Statistics Finland. Information about CHD and other disease morbidity before and during the follow-up was obtained from the Registry of Specially Refunded Drugs of the Finnish Social Insurance Institution (SII). Coxs proportional-hazards models were used to estimate the risk of CHD morbidity related to the use of calcium supplements. At baseline, 2723 women reported current use of calcium or calcium+D supplementation. During the follow-up, CHD was diagnosed in 513 women. Compared to non-users of calcium/calcium+D supplements, the multivariate adjusted hazard ratio (HR) of CHD was 1.24 (95% CI 1.02-1.52) in women who used these supplements. The multivariate adjusted HR for CHD morbidity in postmenopausal women who used calcium/calcium+D supplements was 1.26 (95% CI 1.01-1.57). CONCLUSIONS Calcium or calcium+D supplementation appears to increase the risk of CHD among women before old age.

Relationships between risk factors and fractures differ by type of fracture : A population-based study of 12192 perimenopausal women

Abstract. Relationship between selected factors and fractures according to type of fracture were retrospectively examined in 12192 women aged 47–56 years responding to the baseline postal enquiry of the Kuopio Osteoporosis Study, Finland, in 1989. A total of 1358 women reported fractures sustained during the previous 9.4 years, i.e. at ages 38–57 years. The incidence of fractures per 1000 person-years was 17.2 after menopause and 9.5 before (p < 0.0001). The adjusted fracture risk was elevated in smokers versus non-smokers (OR: 1.5; (95%CI = 1.3–1.9) and in those with chronic health disorders versus the healthy (OR = 1.3; 95% CI 1.1–1.5). Long-term work disability was associated with fractures independently of health disorders (OR = 1.3; 95% CI 1.1–1.6). Anthropometric measures were not associated with the overall fracture risk. Menopause was strongly and linearly related to wrist fracture but not to ankle fracture. A 1 SD increase in body mass index decreased the risk of wrist fracture by 21% (p = 0.0001) but increased that of ankle fracture by 24% (p = 0.002). Smoking was related to ankle fracture (OR = 2.2; 95% CI 1.6–3.2) but not to wrist fracture (OR = 0.9; 95% CI 0.6–1.4). Health disorders were more markedly associated with fractures other than those of the wrist or ankle. Relationships between several risk factors and pre- and perimenopausal fractures vary by type of fracture. This may affect, for example, the comparability of studies with varying fracture profiles.

Does lactose intolerance predispose to low bone density? A population-based study of perimenopausal finnish women

The relationship of lactase malabsorption to osteoporosis is unclear. We examined the relationship of self-reported lactose intolerance (LI) to bone mineral density (BMD) in perimenopausal Finnish women. A random population sample of 2025 women aged 48-59, who underwent spinal and femoral BMD measurement with dual X-ray absorptiometry in Kuopio, Finland during 1989-1991 formed the study population. Out of these women, 162 women reported LI. The mean dairy calcium intake was 558 mg/day in women with LI and 828 mg/day in other women (p < 0.0001). The mean spinal BMDs were 1.097 and 1.129 g/cm2 (-2.8%) (p = 0.016) and the mean femoral BMDs were 0.906 and 0.932 g/cm2 (-2.8%) (p = 0.012) for the LI and other women, respectively. After adjusting for weight, age, years since menopause, and the history of hormone replacement therapy, these differences changed to -2.7% (p = 0.016) for the spinal and -2.4% (p = 0.012) for the femoral BMD, respectively. Dairy calcium intake was an independent determinant of femoral BMD. The addition of calcium intake variables into the multivariate model did not affect the spinal BMD difference, but weakened the femoral BMD difference to -1.9% (p = 0.075). Our results suggest that LI slightly reduces perimenopausal BMD, possibly through reduced calcium intake.

Osteoporosis risk factors, gynaecological history and fractures in perimenopausal women — the results of the baseline postal enquiry of the Kuopio Osteoporosis Risk Factor and Prevention Study

The Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) Study examines the risk factors of osteoporosis, the relationship of risk factors to bone density and fractures, as well as the possibility to prevent bone loss by administering certain hormones. The baseline postal enquiry in 1989 was sent to all the 14,220 women aged 47-56 years residing in the Kuopio Province, Finland. The questionnaire included questions about their gynaecological history, physical exercise and smoking habits, calcium intake, body weight and height, history of bone fractures, health disorders, their current and previous use of drugs, as well as their willingness to participate in bone densitometry and in a clinical hormone trial. The response rate was 92.8%. In all, 56% reported some previous use of female hormones. Strong contraindications for oestrogen replacement therapy were found in 9.3% of the women. Almost half of the respondents reported lack of regular physical exercise, 11.9% were smokers, and 17.0% reported a calcium intake from milk products of less than 500 mg daily. The incidence of fractures increased steadily with age. The incidence of premenopausal fractures within the last 10 years was 7.65 per 1000 person/years and that of postmenopausal fractures was 17.40 per 1000 person/years (P = 0.000). The effect of menopause on fracture incidence was stronger than the effect of a 5-year age increase. Of the respondents, 84.4% were willing to participate in bone densitometry and 68.3% for long-term prevention of osteoporosis with oestrogen.

Risk Factors for Perimenopausal Distal Forearm Fracture

Abstract: 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.

Lactose intolerance associated with fractures of weight-bearing bones in finnish women aged 38–57 years

Lactose intolerance (LI) often results in decreased calcium intake. To test if long-term low intake of calcium affects bone strength, we examined fracture risks related to LI in women aged 38-57 years. The 11,619 Finnish women aged 47-56 years who responded to the baseline postal inquiry of the Kuopio Osteoporosis Risk Factor and Prevention Study in 1989 formed the study population. In all, 896 women reported LI and 1299 women reported a fracture in 1980-1989. Current intake of dairy calcium was lower in women with LI (570 mg/d) than in the other women (850 mg/d) (p < 0.0001). The fracture risk in general was slightly elevated in women with LI compared with the other women, with an odds ratio (OR) (95% CI) of 1.33 (1.09-1.62). However, the fractures at the three most common sites (wrist, ankle, and rib) were not related to LI. In contrast, fractures at the tibia and metatarsal were strongly related to LI with ORs of 3.31 (1.51-7.24) and 2.84 (1.47-5.50), respectively. The adjusted OR for nonankle lower body fractures combined was 2.15 (1.53-3.04), whereas that for all upper body fractures combined was 1.15 (0.88-1.54). The 10 women with LI and a tibial or metatarsal fracture showed a 19% lower femoral BMD than all the other women in the densitometry subsample of 3222 women (p < 0.001). Long-term premenopausal calcium deficiency differentially affects bones with weight-bearing nonankle bones being at the greatest risk of suffering reduced strength.

Lifestyle and other factors predict ankle fractures in perimenopausal women: a population-based prospective cohort study

The Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study examines the risk factors for fractures and low bone density in middle-aged women. In the present study we investigated lifestyle and other risk factors for ankle fracture. The study population consisted of 11,798 women, aged 47-56 years at baseline. During the 5 year follow-up, these women sustained 194 validated malleolar fractures, giving an incidence of 3.4 fractures/1000 person-years. Four independent predictors for malleolar fracture were detected: smoking; multipharmacy; fracture history; and overweight status. The hazard ratio (HR) for positive fracture history was 1.63 (p = 0.005). In women with a body mass index (BMI) of 25-30 kg/m(2) vs. those with a BMI <25 kg/m(2), HR was 1.69 (p = 0.003). Those who used three or more prescribed drugs had an HR of 2.03 (p = 0.0003) vs. those who used no drugs. Smoking had a dose-response effect, with HRs of 1.73 (p = 0.016) in those smoking 1-19 cigarettes/day, and 2.94 (p = 0.001) in those smoking > or =20 cigarettes/day. Lifestyle factors and fracture history appear to be important predictors of ankle fracture.