Cardiovascular diseases and future risk of hip fracture in women.

UNLABELLED: We used a population-based case-control study in women and linkage to the Swedish in-patient register to examine if there is an increased risk of hip fracture after a cardiovascular disease. There was a substantially increased risk of hip fracture after a diagnosis of a cardiovascular disease. INTRODUCTION: Recent data have indicated that cardiovascular diseases (CVDs) might have a relationship to osteoporosis, which may explain the increased risk of mortality after hip fracture. It is uncertain, however, whether there is an increased risk of fracture after any cardiovascular disease and in subgroups of CVDs. The objective of this study was to determine whether there are associations between CVD and future hip fracture risk. Knowledge of the risk pattern would lead to better understanding of common pathologic pathways of osteoporosis and CVD. METHODS: We conducted a population-based case-control study of 1,327 incident hip fracture cases and 3,170 randomly selected population controls among women 50-81 years old in Sweden. Information on cardiovascular and other diseases before the fracture was obtained by linkage to the Swedish National Inpatient Register. Odds ratios (OR) and 95% confidence intervals (CI) where calculated by unconditional logistic regression. RESULTS: Before study entry, CVDs were diagnosed more than twice as commonly among fracture cases (25%) as among controls (12%). Also, after adjustment for variables including several chronic diseases, we found a doubled risk of hip fracture after a CVD event (OR 2.38; 95% CI 1.92-2.94). There was a gradient increase in risk of hip fracture with increasing number of hospitalizations for CVD and highest fracture risk occurred the first year after the CVD event. Hypertension, heart failure, and cerebrovascular lesions remained independent risk factors, with 2- to 3-fold increases in odds ratios, even after mutual adjustments for other CVDs. CONCLUSION: There was a substantially increased risk of hip fracture in women after a diagnosis of a CVD, a finding compatible with the concept of common pathologic pathways for osteoporotic fractures and CVD.

Muscle strength correlates with total body bone mineral density in young women but not in men.

BACKGROUND: Osteoporosis is a growing health problem. One of the proposed reasons for this is a more sedentary lifestyle. The aim of this study was to investigate the associations between muscle strength and total body bone mineral density (TBMD) in young adults at expected peak bone mass. METHODS: Sixty-four women and 61 men (total 125) 21 years of age were included. Handgrip strength, isokinetic knee-flexion and -extension muscle strength, TBMD, and body composition were measured. RESULTS: Univariate regression analyses showed that knee flexion and extension explained almost 30% of the variation in TBMD in women, whereas handgrip strength was not associated with TBMD. In men, no correlation between any measures of muscle strength and TBMD was evident. Stepwise regression analysis showed that knee-flexion and -extension muscle strength in women were associated with TBMD, R2=0.27. In men, lean body mass, fat mass, weight, and height were predictors for TBMD, R2=0.43, whereas muscle strength did not affect the prediction of TBMD. CONCLUSIONS: Muscle strength at weight-bearing sites is related to TBMD in women, whereas body composition is related to TBMD in men. The association of lower limb strength on TBMD only in young women indicates a gender difference.

Bone turnover responses to changed physical activity.

The aim of the study was to compare bone turnover in male soccer players with controls and to follow bone turnover with changes in activity level. Serum-osteocalcin (OC), carboxy-terminal propeptide of type I collagen (PICP) and total alkaline phosphatases (tALP) were measured to assess bone formation. Bone resorption was detected by carboxyterminal cross-linked telopeptide of type I collagen (ICTP). Bone turnover of 12 male premier league soccer players (mean age 23 years, range, 17-34) exercising 12 hours/week (range, 8-15) were at the last day of the soccer season compared with 27 age- and gender-matched controls. Bone turnover was followed weekly during a 4-week resting period between two seasons, and a further 10 days following resumption of full training. Data are presented as mean +/- SEM. Both OC (22 +/- 12%) and ICTP (34 +/- 17%) were higher in the players compared with the controls at the end of the season (both P < 0.05, respectively). After 2 weeks of reduced physical activity among the athletes, the PICP levels were 21 +/- 4% (P < 0.05) lower and the ICTP levels 8 +/- 12% higher (P = 0.07) compared with baseline. OC, PICP, and tALP was then no different compared with controls and ICTP was higher than controls (P < 0.001). Ten days within the new season, there was a 23 +/- 5% increase in PICP (P < 0.001) and a 4 +/- 4% decrease in ICTP (P < 0.05) compared with the end of the resting period. In summary, male soccer players have higher bone turnover compared with age- and gender-matched controls. Changes in physical activity level were associated with changes in bone formation and resorption as evaluated by bone markers within weeks, and after 2 weeks rest, ICTP was higher in the athletes than the controls. We conclude that the higher age-related diminution in BMD, previously reported in former soccer players compared with age- and gender-matched controls, may be the result of increased bone resorption, evaluated by ICTP, compared with the controls.

The duration of exercise as a regulator of bone turnover.

The relationship between duration of exercise and serum remodeling markers of bone turnover was evaluated by osteocalcin (OC), carboxy-terminal propeptide of type I collagen (PICP), total and bone-specific alkaline phosphatase (ALP) and carboxyterminal cross-linked telopeptide of type I collagen (ICTP) in 24 male premier league soccer players exercising 12 hours/week (range 8-18), 19 third league players exercising 8 hours/week (range 3-18) and 20 sixth league players exercising 6 hours/week (range 2-10). Twenty-seven volunteers served as controls. Forty-six former male soccer players (mean age 38 years, range 19-47), mean 15 years older than the current players, were compared with 41 matched controls. Data is presented as mean +/- SEM. Active male players had 18 +/- 4% higher OC, 37 +/- 9% higher bone ALP and 36 +/- 7% higher ICTP than controls (all P < 0.01). There were no differences in remodeling markers within the three groups of active players but each group had higher OC and ICTP than controls (both P < 0.05). Former players had no difference in bone remodeling markers compared to matched controls, but 39 +/- 4% lower OC and 69 +/- 8% lower ICTP than active players (both P < 0.001). Duration of activity was correlated with bone ALP and ICTP (both r = 0.3, P < 0.05) in individuals exercising 6 hours/week or less. No correlation was found in those exercising above this level. It seems as if the bone turnover, evaluated by serum bone remodeling markers, adapts to the current activity needed to maintain bone strength, and a duration of exercise above that level seems to confer no additional benefits.

Discordance between the degree of osteopenia and the prevalence of spontaneous vertebral fractures in Crohn's disease.

BACKGROUND: A high prevalence of osteoporosis has been noted in Crohn's disease, but data about fractures are scarce. METHODS: The relationship between low bone mineral density and the prevalence of vertebral fractures was studied in 271 patients with ileo-caecal Crohn's disease in a large European/Israeli study. One hundred and eighty-one currently steroid-free patients with active Crohn's disease (98 completely steroid-naive) and 90 steroid-dependent patients with inactive or quiescent Crohn's disease were investigated by dual X-ray absorptiometry scan of the lumbar spine, a standardized posterior/anterior and lateral X-ray of the thoracic and lumbar spine, and an assessment of potential risk factors for osteoporosis. RESULTS: Thirty-nine asymptomatic fractures were seen in 25 of 179 steroid-free patients (14.0%; 27 wedge, 12 concavity), and 17 fractures were seen in 13 of 89 steroid-dependent patients (14.6%; 14 wedge, three concavity). The prevalence of fractures in steroid-naive patients was 12.4%. The average bone mineral density, expressed as the T-score, of patients with fractures was not significantly different from that of those without fractures (-0.759 vs. -0.837; P=0.73); 55% of patients with fractures had a normal T-score. The bone mineral density was negatively correlated with lifetime steroids, but not with previous bowel resection or current disease activity. The fracture rate was not correlated with the bone mineral density (P=0.73) or lifetime steroid dose (P=0.83); in women, but not in men, the fracture rate was correlated with age (P=0.009). CONCLUSIONS: The lack of correlation between the prevalence of fractures on the one hand and the bone mineral density and lifetime steroid dose on the other necessitates new hypotheses for the pathogenesis of the former.

Use of low potency estrogens does not reduce the risk of hip fracture.

High endogenous sexual hormone levels and use of medium potency estrogens are associated with a reduced risk of hip fracture in postmenopausal women. However, it is not clear if low potency estrogens confer the same benefits as the more widely used forms of menopausal hormone replacement. We examined the association between postmenopausal use of low potency estrogens, mainly estriol, and hip fracture risk in a population-based, case-control study. Using data from mailed questionnaires and telephone interviews, we analyzed the association between low potency estrogen use and hip fracture risk among 1327 cases, 50-81 years of age, and 3262 randomly selected age-matched controls. Ever use of low potency estrogens was reported by 19% of the cases and 23% of controls. Compared to with never users of any hormone replacement therapy, ever users of low potency estrogens had a multivariate odds ratio (OR) for hip fracture of 0.96 (95% confidence interval [CI] 0.67-1.39). Current use was also not associated with a reduction in risk: OR 0.94 (95% CI 0.58-1.53), and longer duration of use was also not associated with a risk reduction. Even current use of the highest dose of oral estriol (2 mg/day) conferred no risk reduction (OR 1.01, 95% CI 0.61-1.67) compared with never use of hormone replacement therapy. After exclusion of ever users of medium potency estrogens from the analyses, we found a risk reduction of fracture among current vaginal low potency estrogen users (multivariate OR 0.67, 95% CI 0.49-0.92). In contrast to medium potency estrogens, low potency estrogens did not confer a substantial overall reduction in hip fracture risk.

Bone mineral density in femoral neck is positively correlated to circulating insulin-like growth factor (IGF)-I and IGF-binding protein (IGFBP)-3 in Swedish men.

Studies on the hormonal regulation of bone metabolism in men have indicated covariation between insulin-like growth factor-I (IGF-I) and sex hormones with bone mineral density (BMD). In this study the relationships between BMD in total body, lumbar spine, femoral neck, distal and ultradistal (UD) radius and circulating levels of IGFs, IGF binding proteins (IGFBPs), and sex steroids were investigated in 55 Swedish men between 22 and 85 (52 +/- 18, mean +/- SD) years of age. BMD in total body, distal and UD radius, and femoral neck was positively correlated with serum IGF-I (r = 0.31 to 0.49), IGF-II (r = 0.32 to 0.48), IGFBP-3 (r = 0.37 to 0.53), and free androgen index (FAI) (r = 0.32 to 0.40), and negatively with IGFBP-1 (r = -0.37 to -0.41) and IGFBP-2 (r = -0.29 to -0.41) levels. A positive correlation was observed between BMD in femoral neck and estradiol/SHBG ratio (r = 0.34, P = 0.01). Age correlated negatively with serum IGF-I, IGF-II, IGFBP-3, FAI, estradiol/SHBG ratio, and BMD in total body, distal and UD radius, and femoral neck, and positively with IGFBP-1, IGFBP-2, and SHBG levels. According to stepwise multiple regression analyses, a combination of weight, IGFBP-3, and testosterone accounted for 43% of the variation in BMD in femoral neck, 34% in ultradistal radius and 48% in total body (P < 0.0001). These findings indicate that sex hormones and the different components of the IGF system are associated with BMD in Swedish men, suggesting that age-related changes in these systems could contribute to the development of osteoporosis in elderly men.

Increased cardiovascular mortality and normalized serum calcium in patients with mild hypercalcemia followed up for 25 years.

BACKGROUND: The natural history of mild hyperparathyroidism is incompletely clarified. METHODS: Consistent hypercalcemia was found in 172 patients (aged 28-86 years) participating in population-based screenings in both 1969 and 1971. Mortality until 1994 was compared with 344 matched, normocalcemic controls from the study population. Altogether, 55 case-control pairs underwent biochemical analysis in 1992, whereas 86 patients had died, 8 were lost to follow-up, and 23 had undergone parathyroid operation. RESULTS: Mortality was higher (P = .015) in patients younger than 70 years. Cardiovascular diseases were over-represented causes of death. The hazard ratio for hypercalcemia as an independent cause of cardiovascular mortality was 1.72 (95% CI, 1.24-2.37; P < .001). The initially mild hypercalcemia in patients (2.67 +/- 0.07 mmol/L) decreased over time (P = .0001), whereas the serum calcium value remained constant in the controls. Serum calcium and serum parathyroid hormone values in patients were higher than controls at the follow-up (P < .0001, .01, respectively). All but 17 patients were normocalcemic in 1992, and only 2 (1.4%) developed a serum calcium value higher than 3 mmol/L. CONCLUSIONS: Mild hypercalcemia in patients followed up for more than 2 decades is accompanied by premature cardiovascular death despite trends to spontaneous resolution. The principal cause of hypercalcemia probably is primary hyperparathyroidism, but mechanisms contributing to its regression over time are speculative.

Influence of parity and lactation on hip fracture risk.

Several studies indicate that parity and lactation are associated with modest, short-term bone loss, but the long-term effect on osteoporotic fracture risk is uncertain. The authors therefore analyzed data from a population-based case-control study among Swedish postmenopausal women aged 50-81 years between October 1993 and February 1995. Mailed questionnaires and telephone interviews were used to collect data on 1,328 incident cases with hip fracture and 3,312 randomly selected controls. In age-adjusted analyses, the risk of hip fracture among all women was reduced by 10% per child (95% confidence interval (CI): 5, 14). After multivariate adjustment including body mass index as a covariate, the risk reduction was 5% per child (95% CI: 0, 10). Oral contraceptive use modified the association of parity with hip fracture risk. Among never users of oral contraceptives, the risk of hip fracture was reduced by 8% per child (95% CI: 2, 13), whereas among ever users of oral contraceptives, the risk was in the opposite direction, with an increase in risk by 19% per child (95% CI: 0, 41). After parity was considered, there was no association of duration of lactation period with fracture risk. The authors conclude that parity is modestly associated with a reduced hip fracture risk among women who had not used oral contraceptives previously.

Polymorphisms in the renin-angiotensin system and endothelium-dependent vasodilation in normotensive subjects.

BACKGROUND: Our aim was to test the hypothesis that genes encoding components in the renin-angiotensin system influence endothelial vasodilatory function. METHODS: In 59 apparently healthy, normotensive individuals, endothelium-dependent vasodilation (EDV) and endothelial-independent vasodilation (EIDV) was evaluated by infusing metacholine and sodium nitroprusside into the brachial artery. Forearm blood flow was measured by venous occlusion plethysmography. The ACE insertion (I)/deletion (D) polymorphism, the T174M and M235T angiotensinogen restriction fragments length polymorphisms, the angiotensin II receptor type 1 (AT1R) A1166C, and the aldosterone synthase gene (CYP11B2) C-344T polymorphisms were analysed. RESULTS: When analysing the ACE, the two angiotensinogen and the aldosterone synthase CYP11B2 genotypes independently, no significant association with endothelial vasodilatory function was found. However, a significant reduction in endothelium-dependent vasodilation was observed in the subjects (n=9) with the ACE D allele and the angiotensinogen T174M genotype (P<0.05). Subjects with the AT1R genotype AC showed a reduction in both EDV (P=0.05) and EIDV (P=0.04) when compared with those with the AA genotype. CONCLUSIONS: The subjects with the ACE D allele in combination with the angiotensinogen T174M genotype are associated with a reduced EDV. This together with the observation that the AC AT1R genotype is associated with a reduction in both EDV and EIDV, supports the hypothesis that endothelial vasodilatory function is influenced by genes in the renin-angiotensinogen system.

Cigarette smoking, alcohol consumption, and risk of hip fracture in women.

BACKGROUND: Previous studies regarding the impact of cigarette smoking on the risk of hip fracture in postmenopausal women have been inconsistent, suggesting different effects in different groups. The effect of alcohol intake on fracture risk is puzzling: moderate alcohol intake appears to increase bone density, and its association with hip fracture is not clear. METHODS: To assess the associations of cigarette smoking and alcohol consumption with hip fracture risk among postmenopausal women, we conducted an analysis of a population-based case-control study from Sweden. Cases were postmenopausal women, aged 50 to 81 years, who sustained a hip fracture after minor trauma between October 1, 1993, and February 28, 1995; controls were randomly selected from a population-based register during the same period. A mailed questionnaire requesting information on lifestyle habits and medical history was used 3 months after the hip fracture for cases and simultaneously for controls. Age-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed by means of logistic regression. RESULTS: Of those eligible, 1328 cases (82.5%) and 3312 controls (81.6%) responded. Compared with never smokers, current smokers had an increased risk of hip fracture (age-adjusted OR, 1.66; 95% CI, 1.41-1.95). Duration of smoking-particularly postmenopausal smoking-was more important than the amount smoked. Former smokers had a small increase in risk (age-adjusted OR, 1.15; 95% CI, 0.97-1.37) that decreased with the duration of cessation. The age-adjusted OR for women consuming alcohol was 0.80 (95% CI, 0.69-0.93). CONCLUSIONS: Cigarette smoking is a risk factor for hip fracture among postmenopausal women; risk decreases after cessation. Alcohol consumption has a weak inverse association with risk.

DXA of the hip and heel ultrasound but not densitometry of the fingers can discriminate female hip fracture patients from controls: a comparison between four different methods.

Dual-energy X-ray absorptiometry (DXA) of the proximal femur and in more recent years quantitative ultrasound (QUS) of the heel are the most established methods for assessing hip fracture risk. Measurement of the fingers offers a new approach. We performed DXA of the proximal femur, QUS of the heel and fingers, and radiographic absorptiometry (RA) of the fingers in 87 non-institutionalized women, 65-85 years of age, with a first hip fracture and compared them with 195 randomly selected age-matched controls. Bone mineral density (BMD) of the femoral neck and heel Stiffness Index were significantly lower among cases than among controls (by 15% and 17%, respectively; p < 0.0001), whereas no significant differences were found for finger measurements. When applying the WHO criterion of osteoporosis, 62-98% of the patients were classified as osteoporotic, compared with 19-85% of the controls, depending on method and site. The risks of hip fracture, estimated as odds ratios for every 1 SD reduction in femoral neck BMD, heel Stiffness Index, finger QUS and finger RA, were: 3.6 (95% CI 2.4-5.5), 3.4 (95% CI 2.2-5.0), 1.0 (95% CI 0.7-1.3) and 1.2 (95% CI 0.8-1.6), respectively. Compared with women with normal BMD of the femoral neck, those classified as osteopenic had an odds ratio of hip fracture of 14 (95% CI 2-110), whereas those classified as osteoporotic had an odds ratio of 63 (95% CI 8-501). We conclude that hip DXA and heel QUS have similar capacities to discriminate the risk of a first hip fracture, whereas QUS and RA of the phalanges seem inferior techniques for differentiating female hip fracture patients from controls.

Growth hormone secretion and sensitivity in men with idiopathic osteoporosis.

Previous studies have suggested that insulin-like growth factor-I (IGF-I) and its binding proteins (IGFBPs) have a pathogenetic role in idiopathic osteoporosis. To investigate this question further we compared 20 men with idiopathic osteoporosis with 12 healthy, age-matched men regarding growth hormone (GH) secretion and sensitivity. GH samples were drawn every 30 minutes for 24 hours from 12 of the patients and all controls, and cumulated GH secretion (24 hGH) was derived. Peak GH secretion (peakGH) was provoked by an insulin tolerance test. There were no differences between the groups in serum IGF-I (162 +/- 30 vs 163 +/- 47 micrograms/liter, mean +/- SD), IGFBP-3 (2474 +/- 263 vs 2568 +/- 197 micrograms/liter), 24 hGH (1.34 +/- 1.26 vs 0.79 +/- 0.43 U), or peakGH (53.0 +/- 21.5 vs 44.1 +/- 19.8 mU/liter). Patients and controls were given GH (2.4 U/day) for 1 week. Serum levels of markers for bone turnover increased significantly in both groups, with no difference in response to GH between the groups. The increase in urinary bone resorption markers was only significant in the controls. In the patients, but not in the controls, there were significant positive correlations between indices for GH secretion and markers for bone turnover at baseline and significant negative correlations with relative changes in bone markers during GH treatment. In this study no difference in GH secretion was found between men with idiopathic osteoporosis and controls, but the findings suggest that the GH/IGF-I axis could play a regulatory role in bone metabolism in men with this condition.

Interleukin (IL)-13 and IL-4 inhibit proliferation and stimulate IL-6 formation in human osteoblasts: evidence for involvement of receptor subunits IL-13R, IL-13Ralpha, and IL-4Ralpha.

Interleukin-13 (IL-13) inhibits cell proliferation and stimulates interleukin-6 (IL-6) formation in isolated human osteoblasts (hOBs). Because the related cytokine, interleukin-4 (IL-4), is known to exert effects similar to IL-13 in other tissues, and because IL-4 has been implicated as a regulator of bone metabolism, we compared the effects of IL-13 and IL-4 on cell proliferation, IL-6 synthesis, the expression of osteoblastic phenotypic markers in hOB cultures. Also, the receptor proteins mediating these effects in hOBs have been partly characterized. IL-4 and IL-13 dose-dependently inhibited [(3)H]-thymidine incorporation into the DNA of human osteoblasts and stimulated secretion of IL-6 into culture supernatants. IL-13 and IL-4 also increased the mRNA levels of IL-6, as measured by RNAse protection assay. Furthermore, IL-13 and IL-4 dose-dependently enhanced alkaline phosphatase (ALP) activity, but did not affect osteocalcin or collagen type I synthesis. IL-4 was tenfold more potent than IL-13 in inducing both ALP activity and IL-6 secretion, whereas the cytokines were equipotent as inhibitors of cell proliferation. The expression of mRNA for receptor subunits previously implicated in IL-4 and IL-13 signaling was investigated by reverse transcriptase-polymerase chain reaction. IL-13R, IL-13Ralpha, and IL-4Ralpha mRNA were repeatedly detected in hOBs, whereas mRNA for IL-2Rgamma(C) was not detected. Receptor-blocking antibodies to IL-4Ralpha inhibited the induction of IL-6 formation by both IL-4 and IL-13, indicating that both cytokines utilize this receptor subunit in signaling. However, the antibodies did not affect the IL-4/-13-induced inhibition of [(3)H]-thymidine incorporation or the stimulation of alkaline phosphatase (ALP), suggesting that IL-4Ralpha does not mediate these effects of IL-4/-13 in hOBs. We conclude that the cytokines IL-13 and IL-4, through sharing of receptor components, induce similar effects on hOBs, causing inhibition of cell proliferation, stimulation of IL-6, and enhanced ALP activity.

Almost all institutionalized women are osteoporotic, when measured by heel and finger ultrasound.

OBJECTIVES: Since there is a need for simple methods to identify individuals with osteoporosis, we investigated bone status (heel and finger) with ultrasound in an institutionalized elderly population and studied the association between these measures, risk factors for osteoporosis and prevalent osteoporotic fractures. DESIGN: Cross-sectional study. Subjects. Nursing home residents, 237 women and 84 men, mean age 84 years. RESULTS: Altogether 82% of those eligible could undergo heel ultrasound, 65% finger ultrasound and 41% measurements at both sites. Using a transcription of the WHO criterion of osteoporosis, 95% of the women who underwent heel ultrasound were classified as osteoporotic (mean T-score = -4.8) and 92% had Z-scores below zero (mean Z-score=-1.6), whereas 51% of the men were osteoporotic (mean T-score=-2.6) and 77% had Z-scores below zero (mean Z-score=-1.3). Based on finger ultrasound measurements, 99% of the women were classified as osteoporotic (mean T-score=-5.0) and 93% had Z-scores below zero (mean -1.6). The variations in ultrasound values were only moderately explained by age, current weight and walking ability. Amongst women, the association with a prevalent osteoporotic fracture decreased by 43% (95% CI=10-63%) for every SD increase in speed of sound (SOS) of the heel, but no such relationship was found for finger SOS. CONCLUSIONS: Our results from ultrasound measurements at two different anatomical sites indicate that virtually all institutionalized elderly women could be classified as osteoporotic, when measured by these techniques.

Body size and hip fracture risk. Swedish Hip Fracture Study Group.

The objective of this population-based case-control study was to determine the independent association between height, weight at different ages and adult weight change on hip fracture risk, and the joint effects of these factors. The study base comprised postmenopausal women 50-81 years of age who resided in six counties in Sweden during the period October 1993 to February 1995. The study included 1,327 cases with an incident hip fracture and 3,262 randomly selected controls. We obtained information on body measures and other factors possibly related to hip fracture through mailed questionnaires and telephone interviews. Height and weight change were dominant risk factors. Tall women (> or = 169 cm) had an odds ratio of 3.16 (95% confidence interval = 2.47-4.05) compared with women shorter than 159 cm. Weight gain during adult life was strongly protective: compared with those with moderate weight change (-3 to 3 kg), those with substantial weight gain (> or =12 kg) had a markedly decreased risk of hip fracture (odds ratio = 0.35; 95% confidence interval = 0.27-0.45), whereas weight loss was associated with an increased risk. Weight change retained important effects among all subjects, even after controlling for current weight and weight at age 18. In contrast, among women who gained weight, the separate effects of current weight and weight at age 18 were small or absent. Among women who lost weight, both current weight and weight at age 18 had effects that remained after controlling for weight change. Adult weight change and height are dominant body size risk factors for hip fracture. Weight loss vs weight changes demarcates different patterns of hip fracture risk.

Physical activity and hip fracture: a population-based case-control study. Swedish Hip Fracture Study Group.

BACKGROUND: A growing body of literature suggests that physical activity may be a protective factor against hip fracture. METHODS: To study the association between hip fracture risk and recreational physical activity at various ages, changes in activity during adult life, occupational physical activity and how risks vary by adult weight change, we performed a population-based case-control study among postmenopausal women aged 50-81 years residing in six counties in Sweden in 1993-1995. The analysis consisted of 1327 women with hip fracture and 3262 randomly selected controls. Information on leisure physical activity before age 18, at 18-30 years and during recent years was based on a questionnaire. Data on occupational physical activity were collected through an independent classification of job titles obtained from record linkage with census data from 1960, 1970 and 1980. RESULTS: There was a protective effect of recent leisure physical activity. Compared to women who reported no leisure activity, the odds ratios (OR) were 0.79 (95% CI: 0.62-1.00), 0.67 (95% CI: 0.54-0.84) and 0.48 (95% CI: 0.39-0.60) for women who exercised <1 h per week, 1-2 h per week, and 3+ h per week, respectively. These decreased OR were more pronounced in women who had lost weight after 18 years of age than in those who had gained weight. Women with high physical activity at both 18-30 years and during recent years did not have a stronger protection than those with isolated high activity late in life, after accounting for recent activity. Occupational physical activity was not associated with hip fracture risk in this study. CONCLUSIONS: Recent physical activity is protective against hip fracture. The protective effect is most pronounced in women who had lost weight after age 18.

Hypocalcemia and parathyroid hormone secretion in critically ill patients.

OBJECTIVE: To investigate possible causes of hypocalcemia and to assess parathyroid hormone (PTH) secretion in intensive care unit (ICU) patients. DESIGN: Combined cross-sectional and prospective study. SETTING: ICU in a university hospital. PATIENTS: Thirteen patients with sepsis and 13 patients who underwent major surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Calcium metabolic indices were investigated during the first 24 hrs in the ICU and after 2 days. Eight of the surgical patients and five of the septic patients were subjected to a citrate/calcium infusion on day 1 in the ICU, to study the dynamics of PTH secretion. The blood ionized calcium (Ca2+) concentration was generally low in the septic patients (mean +/- SD, 1.03+/-0.08 mmol/L; reference value, 1.10-1.30) and increased, but not normalized, after 2 days. Hypocalcemia was only occasionally seen in the surgical patients. In the septic patients, urinary excretion of calcium was low; and, in both patient groups, elevated concentrations of two markers of bone resorption, deoxypyridinoline and ICTP (serum carboxy-terminal cross-linked telopeptide of type I collagen), were found. In cases of sepsis, the concentrations of proinflammatory cytokines were high (394+/-536 pg/mL for tumor necrosis factor-alpha and 5676+/-5190 pg/mL for interleukin-6, both normally <10-20). The Ca2+ concentration was inversely related to tumor necrosis factor-alpha and interleukin-6 (r2 = .35-.42; p<.01), as well as to procalcitonin (r2 = .71; p<.01). Despite normocalcemia in the surgical patients, serum PTH concentrations were elevated in both patient groups (97 and 109 ng/L) (reference value, <55 ng/L), both on day 1 and day 3 in the ICU. The citrate/calcium infusion revealed an increased secretory response of PTH to lowered Ca2+ concentrations in both groups of patients (p<.05), when compared with matched healthy controls. CONCLUSION: Hypocalcemia was common in septic ICU patients and was not the result of an increased urinary excretion of calcium or of an attenuated bone resorption, but seemed related to the inflammatory response. An increased PTH secretion was found in both patient groups.

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.