Teriparatide and pelvic fracture healing: a phase 2 randomized controlled trial.

Pelvic fracture patients were randomized to blinded daily subcutaneous teriparatide (TPTD) or placebo to assess healing and functional outcomes over 3 months. With TPTD, there was no evidence of improved healing by CT or pain reduction; however, physical performance improved with TPTD but not placebo (group difference p < 0.03). INTRODUCTION: To determine if teriparatide (20 µg/day; TPTD) results in improved radiologic healing, reduced pain, and improved functional outcome vs placebo over 3 months in pelvic fracture patients. METHODS: This randomized, placebo-controlled study enrolled 35 patients (women and men >50 years old) within 4 weeks of pelvic fracture and evaluated the effect of blinded TPTD vs placebo over 3 months on fracture healing. Fracture healing from CT images at 0 and 3 months was assessed as cortical bridging using a 5-point scale. The numeric rating scale (NRS) for pain was administered monthly. Physical performance was assessed monthly by Continuous Summary Physical Performance Score (based on 4 m walk speed, timed repeated chair stands, and balance) and the Timed Up and Go (TUG) test. RESULTS: The mean age was 82, and >80% were female. The intention to treat analysis showed no group difference in cortical bridging score, and 50% of fractures in TPTD-treated and 53% of fractures in placebo-treated patients were healed at 3 months, unchanged after adjustment for age, sacral fracture, and fracture displacement. Median pain score dropped significantly in both groups with no group differences. Both CSPPS and TUG improved in the teriparatide group, whereas there was no improvement in the placebo group (group difference p < 0.03 for CSPPS at 2 and 3 months). CONCLUSION: In this small randomized, blinded study, there was no improvement in radiographic healing (CT at 3 months) or pain with TPTD vs placebo; however, there was improved physical performance in TPTD-treated subjects that was not evident in the placebo group.

Vertebral fracture assessment (VFA) for osteoporosis screening in US postmenopausal women: is it cost-effective?

Vertebral fracture assessment (VFA) is cost-effective when it was incorporated in the routine screening for osteoporosis in community-dwelling women aged ≥ 65 years, which support guidelines, such as the National Osteoporosis Foundation (NOF) for the diagnostic use of VFA as an important addition to fracture risk assessment. INTRODUCTION: To evaluate the cost-effectiveness of VFA as a screening tool to reduce future fracture risk in US community-dwelling women aged ≥ 65 years. METHODS: An individual-level state-transition cost-effectiveness model from a healthcare perspective was constructed using derived data from published literature. The time horizon was lifetime. Five screening strategies were compared, including no screening at all, central dual-energy X-ray absorptiometry (DXA) only, VFA only, central DXA followed by VFA if the femoral neck T-score (FN-T) ≤ - 1.5, or if the FN-T ≤ - 1.0. Various initiation ages and rescreening intervals were evaluated. Oral bisphosphonate treatment for 5-year periods was assumed. Incremental cost-effectiveness ratios (2017 US dollars per quality-adjusted life-year (QALY) gained) were used as the outcome measure. RESULTS: The incorporation of VFA slightly increased life expectancy by 0.1 years and reduced the number of subsequent osteoporotic fractures by 3.7% and 7.7% compared with using DXA alone and no screening, respectively, leading to approximately 30 billion dollars saved. Regardless of initiation ages and rescreening intervals, central DXA followed by VFA if the FN-T ≤ - 1.0 was most cost-effective ($40,792 per QALY when the screening is initiated at age 65 years and with rescreening every 5 years). Results were robust to change in VF incidence and medication costs. CONCLUSION: In women aged ≥ 65 years, VFA is cost-effective when it was incorporated in routine screening for osteoporosis. Our findings support the National Osteoporosis Foundation (NOF) guidelines for the diagnostic use of VFA as an important addition to fracture risk assessment.

Factors associated with the contemplative stage of readiness to initiate osteoporosis treatment.

We investigated the factors associated with readiness for initiating osteoporosis treatment in women at high risk of fracture. We found that women in the contemplative stage were more likely to report previously being told having osteoporosis or osteopenia, acknowledge concern about osteoporosis, and disclose prior osteoporosis treatment. INTRODUCTION: Understanding factors associated with reaching the contemplative stage of readiness to initiate osteoporosis treatment may inform the design of behavioral interventions to improve osteoporosis treatment uptake in women at high risk for fracture. METHODS: We measured readiness to initiate osteoporosis treatment using a modified form of the Weinstein Precaution Adoption Process Model (PAPM) among 2684 women at high risk of fracture from the Activating Patients at Risk for OsteoPOroSis (APROPOS) clinical trial. Pre-contemplative participants were those who self-classified in the unaware and unengaged stages of PAPM (stages 1 and 2). Contemplative participants were those in the undecided, decided not to act, or decided to act stages of PAPM (stages 3, 4, and 5). Using multivariable logistic regression, we evaluated participant characteristics associated with levels of readiness to initiate osteoporosis treatment. RESULTS: Overall, 24% (N = 412) self-classified in the contemplative stage of readiness to initiate osteoporosis treatment. After adjusting for age, race, education, health literacy, and major osteoporotic fracture in the past 12 months, contemplative women were more likely to report previously being told they had osteoporosis or osteopenia (adjusted odds ratio [aOR] (95% CI) 11.8 (7.8-17.9) and 3.8 (2.5-5.6), respectively), acknowledge concern about osteoporosis (aOR 3.5 (2.5-4.9)), and disclose prior osteoporosis treatment (aOR 4.5 (3.3-6.3)) than women who self-classified as pre-contemplative. CONCLUSIONS: For women at high risk for future fractures, ensuring women's recognition of their diagnosis of osteoporosis/osteopenia and addressing their concerns about osteoporosis are critical components to consider when attempting to influence stage of behavior transitions in osteoporosis treatment.

Self-perception of fracture risk: what can it tell us?

In this study, we report that self-perception of fracture risk captures some aspect of fracture risk not currently measured using conventional fracture prediction tools and is associated with improved medication uptake. It suggests that adequate appreciation of fracture risk may be beneficial and lead to greater healthcare engagement and treatment. INTRODUCTION: This study aimed to assess how well self-perception of fracture risk, and fracture risk as estimated by the fracture prediction tool FRAX, related to fracture incidence and uptake and persistence of anti-osteoporosis medication among women participating in the Global Longitudinal study of Osteoporosis in Women (GLOW). METHODS: GLOW is an international cohort study involving 723 physician practices across 10 countries in Europe, North America and Australia. Aged ≥ 55 years, 60,393 women completed baseline questionnaires detailing medical history, including co-morbidities, fractures and self-perceived fracture risk (SPR). Annual follow-up included self-reported incident fractures and anti-osteoporosis medication (AOM) use. We calculated FRAX risk without bone mineral density measurement. RESULTS: Of the 39,241 women with at least 1 year of follow-up data, 2132 (5.4%) sustained an incident major osteoporotic fracture over 5 years of follow-up. Within each SPR category, risk of fracture increased as the FRAX categorisation of risk increased. In GLOW, only 11% of women with a lower baseline SPR were taking AOM at baseline, compared with 46% of women with a higher SPR. AOM use tended to increase in the years after a reported fracture. However, women with a lower SPR who were fractured still reported lower AOM rates than women with or without a fracture but had a higher SPR. CONCLUSIONS: These results suggest that SPR captures some aspect of fracture risk not currently measured using conventional fracture prediction tools and is also associated with improved medication uptake.

Disease-specific perception of fracture risk and incident fracture rates: GLOW cohort study.

UNLABELLED: Accurate patient risk perception of adverse health events promotes greater autonomy over, and motivation towards, health-related lifestyles. INTRODUCTION: We compared self-perceived fracture risk and 3-year incident fracture rates in postmenopausal women with a range of morbidities in the Global Longitudinal study of Osteoporosis in Women (GLOW). METHODS: GLOW is an international cohort study involving 723 physician practices across ten countries (Europe, North America, Australasia); 60,393 women aged ≥55 years completed baseline questionnaires detailing medical history and self-perceived fracture risk. Annual follow-up determined self-reported incident fractures. RESULTS: In total 2,945/43,832 (6.8%) sustained an incident fracture over 3 years. All morbidities were associated with increased fracture rates, particularly Parkinson's disease (hazard ratio [HR]; 95% confidence interval [CI], 3.89; 2.78-5.44), multiple sclerosis (2.70; 1.90-3.83), cerebrovascular events (2.02; 1.67-2.46), and rheumatoid arthritis (2.15; 1.53-3.04) (all p < 0.001). Most individuals perceived their fracture risk as similar to (46%) or lower than (36%) women of the same age. While increased self-perceived fracture risk was strongly associated with incident fracture rates, only 29% experiencing a fracture perceived their risk as increased. Under-appreciation of fracture risk occurred for all morbidities, including neurological disease, where women with low self-perceived fracture risk had a fracture HR 2.39 (CI 1.74-3.29) compared with women without morbidities. CONCLUSIONS: Postmenopausal women with morbidities tend to under-appreciate their risk, including in the context of neurological diseases, where fracture rates were highest in this cohort. This has important implications for health education, particularly among women with Parkinson's disease, multiple sclerosis, or cerebrovascular disease.

Skeletal effects of nutrients and nutraceuticals, beyond calcium and vitamin D.

There is a need to understand the role of nutrition, beyond calcium and vitamin D, in the treatment and prevention of osteoporosis in adults. Results regarding soy compounds on bone density and bone turnover are inconclusive perhaps due to differences in dose and composition or in study population characteristics. The skeletal benefit of black cohosh and red clover are unknown. Dehydroepiandrosterone (DHEA) use may benefit elderly individuals with low serum dehydroepiandrosterone-sulfate levels, but even in this group, there are inconsistent benefits to bone density (BMD). Higher fruit and vegetable intakes may relate to higher BMD. The skeletal benefit of flavonoids, carotenoids, omega-3-fatty acids, and vitamins A, C, E and K are limited to observational data or a few clinical trials, in some cases investigating pharmacologic doses. Given limited data, it would be better to get these nutrients from fruits and vegetables. Potassium bicarbonate may improve calcium homeostasis but with little impact on bone loss. High homocysteine may relate to fracture risk, but the skeletal benefit of each B vitamin is unclear. Magnesium supplementation is likely only required in persons with low magnesium levels. Data are very limited for the role of nutritional levels of boron, strontium, silicon and phosphorus in bone health. A nutrient rich diet with adequate fruits and vegetables will generally meet skeletal needs in healthy individuals. For most healthy adults, supplementation with nutrients other than calcium and vitamin D may not be required, except in those with chronic disease and the frail elderly.

Skeletal effects of vitamin D supplementation in postmenopausal black women.

Black women have lower serum 25-hydroxyvitamin D (25[OH]D) levels and higher parathyroid hormone (PTH) levels than white peers but lower bone turnover, suggesting skeletal resistance to PTH. Our objective was to determine if vitamin D supplementation (1,000 IU/day) would prevent bone loss and whether vitamin D receptor (VDR) polymorphisms modify the response. We performed a 2-year randomized, controlled, double-blind study of 1,000 IU vitamin D(3) vs. placebo in postmenopausal black women with serum 25(OH)D levels <20 ng/mL (n = 103). Measurements of 25(OH)D, PTH, and bone turnover were evaluated at baseline and 3, 6, 12, 18, and 24 months. DNA was extracted from peripheral blood leukocytes, and genotyping was conducted using standard techniques. Spine and hip bone mineral density (BMD) was measured at baseline and every 6 months. Serum 25(OH)D increased 11 ng/mL with vitamin D supplementation (p < 0.001), with no change in the placebo group. Vitamin D supplementation produced a significant decline in PTH at 3 months only, with no differences in bone turnover between placebo and vitamin D at any time point. Two-year changes in BMD were not significantly different between placebo- and vitamin D-treated black women at any skeletal site. Despite similar elevations in 25(OH)D, femoral neck BMD was only responsive to vitamin D supplementation in FF subjects (n = 47), not Ff/ff subjects (n = 31). Vitamin D supplementation does not appear to influence bone loss in black women. However, in the FF polymorphism of the VDR gene group, vitamin D supplementation may retard the higher rate of bone loss.

Fragility fractures of the hip and femur: incidence and patient characteristics.

SUMMARY: Using national discharge and medical claims data, we studied the epidemiology of femoral fractures from 1996 to 2006. The annual hip fracture incidence declined from 600/100,000 to 400/100,000, without decline in the more rare femur fractures. Incidence rates for subtrochanteric and femoral shaft fractures were each below 20 per 100,000. INTRODUCTION: This study's purpose is to describe the site-specific epidemiology of femur fractures among people aged 50 and older. METHODS: Using the National Hospital Discharge Survey from 1996 to 2006 and a large medical claims database (MarketScan), we studied epidemiology of all femur fractures. Hip fractures were grouped together; subtrochanteric, shaft, and distal femur fractures were kept separate. RESULTS: In females, the overall hospital discharge rates of hip fracture decreased from about 600/100,00 to 400/100,000 person-years from 1996 to 2006. Subtrochanteric, femoral shaft, and lower femur rates remained stable, each approximately 20 per 100,000 person-years. Similar trends but lower rates existed in males. No significant trends were found in any of these fractures during the more recent years of 2002-2006 (MarketScan data). Using MarketScan, the overall incidence of hip fracture was <300/100,000 person-years; incidence of subtrochanteric and femoral shaft fractures combined was <25/100,000 person-years and distal femur fracture incidence was <18/100,000 person-years in females; rates were lower in males. The incidence of hip and other femur fractures increased exponentially with age. CONCLUSIONS: We found no evidence of an increasing incidence of any femoral fracture. Hip fracture incidence is declining but the incidence of each of the more rare femur fractures (distal to the lesser trochanter) is stable over time.

Relationship between growth hormone in vivo bioactivity, the insulin-like growth factor-I system and bone mineral density in young, physically fit men and women.

CONTEXT: Bone mineral density (BMD) is influenced by growth factors, such as growth hormone (GH) and insulin-like growth factor-I (IGF-I). The in vivo bioassay for GH (bioGH) provides a more physiologically relevant measurement than an in vitro immunoassay, since bioGH is quantified on a biological outcome. OBJECTIVE: To determine if bioGH and components of the IGF-I system were associated with BMD in age-matched men (M; n=41, 19.1+/-0.2 year, 70+/-3 kg, 163+/-25 cm) and women (W; n=39, 18.6+/-0.3 year, 66+/-3 kg, 141+/-15 cm). DESIGN: Blood was analyzed for growth-related hormones [bioGH, immunoreactive growth hormone (iGH), IGF-I and associated binding proteins], and BMD was measured by pDXA, pQCT, and central DXA (spine, hip). For the bioGH assay, hypophysectomizied female Sprague-Dawley rats were injected with a s.c. bolus of either a GH standard or unknown (each subject's plasma) in four daily injections. The tibia was then examined for epiphyseal growth plate width from which bioGH concentrations were extrapolated. RESULTS: M had greater (P<0.05) calcaneal BMD when measured by pDXA (M: 1.27+/-0.02; W: 1.14+/-0.02 g/cm2), while pQCT-assessed BMD at the tibia was not different (M: 777+/-16; W: 799+/-16 g/cm2). bioGH was similar between M (5388+/-800 microg/L) and W (4282+/-643 microg/L) and was not correlated with BMD. The only BMD-related biomarkers in women were acid-labile subunit (ALS; r=0.40) and IGFBP-3 (r=0.42) with DXA-measured spine and femoral neck BMD, and ALS (r=0.47) with pQCT-assessed tibial BMD and cortical thickness, respectively. CONCLUSION: Although bioGH was not associated with BMD, IGF-I and associated binding proteins (IGFBP-3 and ALS) emerged as correlates in W only.

Short-term effects of estrogen, tamoxifen and raloxifene on hemostasis: a randomized-controlled study and review of the literature.

INTRODUCTION: Estrogen therapy (ET), tamoxifen and raloxifene are associated with a two- to three-fold increased risk of venous thrombosis (VT); however, the mechanisms by which each drug increases venous thrombosis propensity are not fully understood. The objectives of this investigation were to compare the effects of these three treatments on hemostasis in a head to head randomized placebo-controlled trial. PATIENTS/METHODS: Ninety-four postmenopausal women were assigned to receive oral estrogen (conjugated equine estrogen [CEE] 0.625 mg, n=23), tamoxifen 20 mg (n=24), raloxifene 60 mg (n=24) or placebo (n=23) daily for 6 months. Blood samples were analyzed for procoagulant factors (prothrombin, factors VII [fVII], VIII [fVIII], IX [fIX] and XI [fXI], D-dimer and von Willebrand factor [vWf]), anticoagulant factors (antithrombin [AT], total and free protein S, protein C and activated protein C [APC] resistance) and fibrinolytic factors (thrombin activatable fibrinolysis inhibitor [TAFI] and plasminogen activator inhibitor-1 [PAI-1]), at baseline and at 6 months of treatment. RESULTS: Estrogen increased factor VII and D-dimer, and decreased antithrombin, total and free protein S and PAI-1. Changes with tamoxifen were distinct from estrogen with increases in factors VIII, IX, vWf and free protein S, and decreases in AT, total protein S, protein C and plasminogen activator inhibitor-1. Raloxifene produced similar effects as tamoxifen, but did not increase factor IX or decrease protein C. CONCLUSIONS: Estrogen, tamoxifen and raloxifene affected hemostasis favoring procoagulation and impairing anticoagulation. The biochemical effects of the selective estrogen receptor modulators (SERMs) were distinct from those of estrogen and differed only subtly from each other.

Resistance to bone resorbing effects of PTH in black women.

Black women have a lower incidence of vertebral and hip fractures than white women, possibly due to differences in skeletal and mineral metabolism. One suggested mechanism is that blacks have decreased skeletal sensitivity to parathyroid hormone (PTH). To test this hypothesis, we infused h(1-34)PTH in healthy premenopausal black (n = 15) and white (n = 18) women over 24 h and measured serum and urine indices of bone turnover and calcium metabolism throughout the infusion. At baseline, the mean 25-hydroxyvitamin D (25(OH)D) concentration was significantly lower in black women (46%). There were also nearly significant trends toward higher PTH and lower urinary calcium and pyridinoline levels in black women. During infusion, there were no racial differences in the mean (1-34)PTH levels achieved or in resultant elevations of serum calcium or 1,25-dihydroxyvitamin D (1,25(OH)2D) levels. Endogenous parathyroid suppression (measured by (1-84)PTH levels) was also similar between blacks and whites. There was an initial decline in urinary calcium/creatinine in both groups with a greater reduction in black women early in the infusion period (p < 0.05 at 8 h). Furthermore, blacks had lower levels of urinary calcium/creatinine throughout the infusion (p < 0.05 group difference). Bone formation markers (carboxy-terminal propeptide of type I procollagen and osteocalcin) decreased within 8 h and continued to decline throughout the infusion with no distinguishable racial differences (p < 0.05 time trend for both). The most dramatic difference between black and white women in response to PTH infusion was represented by the bone resorption markers. Three separate metabolites of bone resorption (cross-linked N-telopeptide of type I collagen, cross-linked C-telopeptide of type I collagen, and free pyridinoline) all showed substantially greater elevations in white (mean peak increments 399, 725, and 43%) compared with black women (mean peak increments 317, 369, and 17%) during the infusion (p < 0.05 group differences for all three variables). These data strongly suggest that blacks have decreased skeletal sensitivity to the acute resorptive effects of increased PTH. This finding indicates that calcium homeostasis may be accomplished in blacks (during times of relative calcium deficiency) by greater conservation of calcium from nonskeletal sources (most likely renal) with relative preservation of skeletal tissue. These differences in calcium economy could account, at least in part, for the increased bone mass and lower incidence of osteoporotic fractures in black women.

Calcium potentiates the effect of estrogen and calcitonin on bone mass: review and analysis.

We reviewed published clinical trials that measured bone mass of postmenopausal women from at least one skeletal site to evaluate whether calcium supplementation influenced the efficacy of estrogens and intranasal calcitonin on bone mass change. We compared results of the administration of oral estrogen or nasal calcitonin in conjuction with additional calcium intake either through diet or supplements compared with those of estrogen or calcitonin alone. Of the 31 published estrogen trials analyzed, 20 modified the diet or used a calcium supplement (total 1183 mg/d) and 11 did not (total 563 mg/d). The mean increase in bone mass of the lumbar spine when estrogen was given alone was 1.3%/y (n = 5) compared with 3.3%/y when estrogen was given in conjunction with calcium (n = 14; P = 0.01). The mean increase in bone mass of the femoral neck with estrogen alone (n = 3) was only 0.9%/y compared with 2.4%/y when calcium was given with estrogen (n = 6; P = 0.04). Similarly, forearm bone mass increased 0.4%/y with estrogen alone (n = 7) compared with 2.1%/y when estrogen was given with calcium (n = 12; P = 0.04). Similar results were found when weighted means were calculated. Of the seven published trials evaluating the effects of 200 IU nasal salmon calcitonin, six also used calcium supplements (total 1466 mg/d) whereas one used calcitonin alone (total 627 mg/d). Bone mass of the lumbar spine increased 2.1% with calcitonin plus calcium supplementation compared with -0.2%/y with calcitonin alone. These results suggest that a high calcium intake potentiates the positive effect of estrogen on bone mass at all skeletal sites and perhaps that of calcitonin on bone mass of the spine.

Constant mineralization density distribution in cancellous human bone.

The degree of mineralization of bone matrix is an important factor in determining the mechanical competence of bone. The remodeling and modeling activities of bone cells together with the time course of mineralization of newly formed bone matrix generate a characteristic bone mineralization density distribution (BMDD). In this study we investigated the biological variance of the BMDD at the micrometer level, applying a quantitative backscattered electron imaging (qBEI) method. We used the mean calcium concentration (Ca(Mean)), the most frequent calcium concentration (Ca(Peak)), and full width at half maximum (Ca(Width)) to characterize the BMDD. In none of the BMDD parameters were statistically significant differences found due to ethnicity (15 African-American vs. 27 Caucasian premenopausal women), skeletal site variance (20 ilium, 24 vertebral body, 13 patella, 13 femoral neck, and 13 femoral head), age (25 to 95 years), or gender. Additionally, the interindividual variance of Ca(Mean) and Ca(Peak), irrespective of biological factors, was found to be remarkably small (SD < 2.1% of means). However, there are significant changes in the BMDD in the case of bone diseases (e.g., osteomalacia) or following clinical treatment (e.g., alendronate). From the lack of intraindividual changes among different skeletal sites we conclude that diagnostic transiliac biopsies can be used to determine the BMDD variables of cancellous bone for the entire skeleton of the patient. In order to quantify deviations from normal mineralization, a reference BMDD for adult humans was calculated using bone samples from 52 individuals. Because we find the BMDD to be essentially constant in healthy adult humans, qBEI provides a sensitive means to detect even small changes in mineralization due to bone disease or therapeutic intervention.

Effect of prior and ongoing raloxifene therapy on response to PTH and maintenance of BMD after PTH therapy.

UNLABELLED: Women with osteoporosis on raloxifene were randomized to 1-34hPTH + raloxifene or raloxifene alone for one year. In the PTH + raloxifene group, bone turnover increased 125-584%, spine BMD increased 9.6%, hip BMD increased 1.2-3.6% and radius BMD declined 4.3%. During the follow-up year, on continued raloxifene, BMD declined slightly at all sites except the femoral neck. INTRODUCTION: The influence of prior antiresorptives on response to 1-34PTH and the ability to maintain BMD gains might differ for antiresorptive agents with different potencies. The objectives were to evaluate biochemical and bone density responses to 1-34PTH in patients on prior and ongoing raloxifene and to determine whether raloxifene maintains bone gains. METHODS: Forty-two postmenopausal women with osteoporosis on raloxifene were randomized to raloxifene alone or 1-34PTH daily for 12 months (continuing raloxifene). Women were then followed for 12 months on raloxifene alone. Bone turnover markers and BMD were measured at baseline and at 3, 6, 12, 18 and 24 months. RESULTS: Biochemical indices increased rapidly during PTH treatment with peak increments of 125-584% for the three markers (p<0.001 vs. baseline). After one year of PTH, mean BMD increases were 9.6% for spine, 2.7% for total hip, 3.6% for trochanter (all p<0.005) and 1.2% in femoral neck (NS), while BMD declined 4.3% in the radius (p=0.003). After PTH withdrawal, on continued raloxifene, BMD declined slightly (0.7-2.9% losses; NS) at all sites, except the femoral neck, where BMD increased modestly (p=0.04). At 24 months, spine and femoral neck BMD remained significantly higher than baseline, while radius BMD remained significantly lower (all p<0.04). CONCLUSION: Substantial gains in BMD of the spine and hip, but not the radius, are seen with one year of PTH treatment in patients on prior raloxifene. After PTH is discontinued, raloxifene partially maintains PTH-induced BMD gains in the spine and hip.

Calcium and vitamin D intake influence bone mass, but not short-term fracture risk, in Caucasian postmenopausal women from the National Osteoporosis Risk Assessment (NORA) study.

UNLABELLED: The impact of calcium and vitamin D intake on bone density and one-year fracture risk was assessed in 76,507 postmenopausal Caucasian women. Adequate calcium with or without vitamin D significantly reduced the odds of osteoporosis but not the risk of fracture in these Caucasian women. INTRODUCTION: Calcium and vitamin D intake may be important for bone health; however, studies have produced mixed results. METHODS: The impact of calcium and vitamin D intake on bone mineral density (BMD) and one-year fracture incidence was assessed in 76,507 postmenopausal Caucasian women who completed a dietary questionnaire that included childhood, adult, and current consumption of dairy products. Current vitamin D intake was calculated from milk, fish, supplements and sunlight exposure. BMD was measured at the forearm, finger or heel. Approximately 3 years later, 36,209 participants returned a questionnaire about new fractures. The impact of calcium and vitamin D on risk of osteoporosis and fracture was evaluated by logistic regression adjusted for multiple covariates. RESULTS: Higher lifetime calcium intake was associated with reduced odds of osteoporosis (peripheral BMD T-score < or =-2.5; OR = 0.80; 95% CI 0.72, 0.88), as was a higher current calcium (OR = 0.75; (0.68, 0.82)) or vitamin D intake (OR = 0.73; 95% CI 0.0.66, 0.81). Women reported 2,205 new osteoporosis-related fractures. The 3-year risk of any fracture combined or separately was not associated with intake of calcium or vitamin D. CONCLUSIONS: Thus, higher calcium and vitamin D intakes significantly reduced the odds of osteoporosis but not the 3-year risk of fracture in these Caucasian women.

Determinants of bone mass and bone size in a large cohort of physically active young adult men.

The determinants of bone mineral density (BMD) at multiple sites were examined in a fit college population. Subjects were 755 males (mean age = 18.7 years) entering the United States Military Academy. A questionnaire assessed exercise frequency and milk, caffeine, and alcohol consumption and tobacco use. Academy staff measured height, weight, and fitness. Calcaneal BMD was measured by peripheral dual-energy x-ray absorptiometry (pDXA). Peripheral-quantitative computed tomography (pQCT) was used to measure tibial mineral content, circumference and cortical thickness. Spine and hip BMD were measured by DXA in a subset (n = 159). Mean BMD at all sites was approximately one standard deviation above young normal (p < 0.05). African Americans had significantly higher hip, spine and heel BMD and greater tibial mineral content and cortical thickness than Caucasians and Asians. In Caucasians (n = 653), weight was a significant determinant of BMD at every skeletal site. Prior exercise levels and milk intake positively related to bone density and size, while caffeine had a negative impact. There was an apparent interaction between milk and exercise in BMD at the heel, spine, hip and tibial mineral content and cortical thickness. Our data confirm the importance of race, body size, milk intake and duration of weekly exercise as determinants of BMD and bone size.

Comparative assessment of bone mineral density of the forearm using single photon and dual X-ray absorptiometry.

Forearm bone mineral density (BMD) was measured at proximal and distal sites by 125I single photon absorptiometry (SPA) and by dual energy X-ray absorptiometry (DXA) in 67 consecutive subjects, aged 18-75 years. Correlations and regression equations between these two techniques were determined. All forearm measurements were significantly correlated with each other (r = 0.599-0.926; P < or = 0.0001). Although SPA and DXA correct for fat in different ways, we found similar correlation and regression equations in women with body mass index measurements above and below the mean. In addition, forearm measurements by both techniques were moderately correlated with vertebral spine and hip BMD. We conclude that overall, SPA forearm measurements in a population can be calibrated to DXA measurements if necessary, and that DXA forearm measurements are as predictive of the remainder of the skeleton as SPA measurements.

A case-control study of hip fracture: evaluation of selected dietary variables and teenage physical activity.

Recent diet, teenage physical activity and teenage calcium consumption were examined as risk factors for hip fracture in a case-control study. Cases were 161 white women admitted to one of 30 participating hospitals with a first hip fracture. Controls included 168 white women from general and orthopedic surgical services frequency-matched to cases by age group and hospital. Information on exposure to possible risk factors was obtained by in-person interview. No association was found between recent intake of calcium, phosphorus, protein, vitamin C or caffeine and hip fracture. Also, teenage calcium intake and milk drinking were not related to hip fracture risk. Recreational activities in adolescence and early adulthood appeared to afford protection against hip fracture. The highest quartile of recreational activity (greater than or equal to 4 times/week) was associated with an odds ratio of 0.24 (95% confidence interval 0.08-0.75) relative to the lowest quartile (less than 1 time/week).

Cancer near the Three Mile Island nuclear plant: radiation emissions.

As a public charge, cancers among the 159,684 residents living within a 10-mile (16-km) radius of the Three Mile Island nuclear plant were studied relative to releases of radiation during the March 28, 1979, accident as well as to routine plant emissions. The principal cancers considered were leukemia and childhood malignancies. Estimates of the emissions delivered to small geographic study tracts were derived from mathematical dispersion models which accounted for modifying factors such as wind and terrain; the model of accident emissions was validated by readings from off-site dosimeters. Incident cancers among area residents for the period 1975-1985 (n = 5,493) were identified by a review of the records at all local and regional hospitals; preaccident and postaccident trends in cancer rates were examined. For accident emissions, the authors failed to find definite effects of exposure on the cancer types and population subgroups thought to be most susceptible to radiation. No associations were seen for leukemia in adults or for childhood cancers as a group. For leukemia in children, the odds ratio was raised, but cases were few (n = 4), and the estimate was highly variable. Moreover, rates of childhood leukemia in the Three Mile Island area are low compared with national and regional rates. For exposure to routine emissions, the odds ratios were raised for childhood cancers as a whole and for childhood leukemia, but confidence intervals were wide and included 1.0. For leukemia in adults, there was a negative trend. Trends for two types of cancer ran counter to expectation. Non-Hodgkin's lymphoma showed raised risks relative to both accident and routine emissions; lung cancer (adjusted only indirectly for smoking) showed raised risks relative to accident emissions, routine emissions, and background gamma radiation. Overall, the pattern of results does not provide convincing evidence that radiation releases from the Three Mile Island nuclear facility influenced cancer risk during the limited period of follow-up.

Cancer rates after the Three Mile Island nuclear accident and proximity of residence to the plant.

BACKGROUND: In the light of a possible link between stress and cancer promotion or progression, and of previously reported distress in residents near the Three Mile Island (TMI) nuclear power plant, we attempted to evaluate the impact of the March 1979 accident on community cancer rates. METHODS: Proximity of residence to the plant, which related to distress in previous studies, was taken as a possible indicator of accident stress; the postaccident pattern in cancer rates was examined in 69 "study tracts" within a 10-mile radius of TMI, in relation to residential proximity. RESULTS: A modest association was found between postaccident cancer rates and proximity (OR = 1.4; 95% CI = 1.3, 1.6). After adjusting for a gradient in cancer risk prior to the accident, the odds ratio contrasting those closest to the plant with those living farther out was 1.2 (95% CI = 1.0, 1.4). A postaccident increase in cancer rates near the Three Mile Island plant was notable in 1982, persisted for another year, and then declined. Radiation emissions, as modeled mathematically, did not account for the observed increase. CONCLUSION: Interpretation in terms of accident stress is limited by the lack of an individual measure of stress and by uncertainty about whether stress has a biological effect on cancer in humans. An alternative mechanism for the cancer increase near the plant is through changes in care-seeking and diagnostic practice arising from postaccident concern.