Bone Mineral Density Status Research Articles

Adiposity and bone mineral density of Chilean elderly women in relation to toll-like receptor 4 gene polymorphisms

Background: It has been proposed that the toll-like receptor-4 gene (TLR4) may participate in the development of obesity and osteoporosis, in addition to its well-known role in the immune response. On the other hand, the adipose tissue of obese subjects shows an increased expression of the proinflammatory cytokine, tumour necrosis factor-alpha (TNF-α), which is released after lipopolysaccharide recognition by TLR4.Aim: To estimate the allele/genotype frequencies and linkage disequilibrium measures of Asp299Gly and Thr399Ile polymorphisms of the TLR4 gene in the Chilean elderly population, and to screen for their association with variables related to adiposity or bone mineral density.Subjects and methods: The study group included 227 unrelated Chilean elderly women (61–95 years) recruited from a population-based sample. Adiposity and bone mineral density measures were obtained using dual-energy X-ray absorptiometry.Results: The allele frequencies for TNF −308A, TLR4 299Gly and TLR4 −399Ile were 9.3%, 4.6% and 4.4%, respectively, with Asp299Gly and Thr399Ile being in strong linkage disequilibrium (D′ = 0.88). Although seriously restricted by the low frequency of the allele variants, no relevant association between genotypes and adiposity-related variables were found. Likewise, no significant association between osteoporosis status (categorized as osteoporosis, osteopenia or normal status) with TLR4 Asp299Gly or TNF −308G>A genotypes was found.Conclusion: It is unlikely that TLR4 Asp299Gly, TLR4 Thr399Ile or TNF −308G>A polymorphisms have a major influence on adiposity, bone mineral density or osteoporosis status in Chilean elderly women.

Exercise maintains bone density at spine and hip EFOPS: a 3-year longitudinal study in early postmenopausal women

It is an important aim in the prevention of osteoporosis to stop or decelerate bone loss during the early postmenopausal years. Here we report on results of the 3-year EFOPS exercise trial in osteopenic women. The exercise strategy emphasized low-volume high-resistance strength training and high-impact aerobics. Forty-eight fully compliant women (55.1+/-3.3 years) with no medication or illness affecting bone metabolism participated in the exercise group (EG); 30 women (55.5+/-3.0 years) served as non-training controls (CG). At baseline there were no significant between-group differences with respect to physical fitness, bone mineral density, pain and nutritional status. The training consisted of two group training and two home training sessions per week. The study participants of both groups were individually supplemented with calcium and vitamin D (cholecalciferol). Bone mineral density (BMD) was measured by DXA at the lumbar spine, proximal femur and distal forearm and by QCT at the lumbar spine. Speed of sound and broadband ultrasound attenuation were determined at the calcaneus by quantitative ultrasound (QUS). Pain frequency and intensity at different skeletal sites were assessed via questionnaire. After 38 months, the following within-group changes were measured: DXA lumbar spine, EG: 0.8% n.s.; CG: -3.3% P<0.001; QCT trabecular ROI, EG: 1.1% n.s; CG: -7.7% P<0.001; QCT cortical ROI, EG: 5.3% P<0.001; CG: -2.6% P<0.001; DXA total hip: EG: -0.2% n.s; CG -1.9%, P<0.001; DXA distal forearm, EG: -2.8% P<0.001; CG: -3.8% P<0.001; BUA, EG: -0.3% n.s; CG -5.4% P<0.001; SOS, EG: 0.3% n.s; CG -1.0% P<0.001. At year 3 between-group differences relative to the exercise group were: DXA lumbar spine: 4.1% P<0.001; QCT trabecular ROI: 8.8% P<0.001; QCT cortical ROI: 7.9% P<0.001; DXA total hip: 2.1%, P<0.001; DXA distal forearm: 1.0% n.s.; BUA: 5.8% P<0.05; SOS: 1.3% P<0.001. Pain frequency and intensity in the spine significantly decreased in the exercise group and increased in the control group, while no between-group differences were detected in the main joints. In summary, over a period of 3 years our low-volume/high-intensity exercise program was successful to maintain bone mineral density at the spine, hip and calcaneus, but not at the forearm.

Vitamin D and bone mineral density status of healthy schoolchildren in northern India

Current data on the prevalence of vitamin D deficiency in India are scarce. We assessed the calcium-vitamin D-parathyroid hormone axis in apparently healthy children from 2 different socioeconomic backgrounds in New Delhi, India. Clinical evaluation for evidence of vitamin D deficiency was carried out in 5137 apparently healthy schoolchildren, aged 10-18 y, attending lower (LSES) and upper (USES) socioeconomic status schools. Serum calcium, inorganic phosphorus, alkaline phosphatase, 25-hydroxyvitamin D [25(OH)D], and immunoreactive parathyroid hormone were measured in 760 children randomly selected from the larger cohort. Bone mineral density of the forearm and the calcaneum was measured in 555 children by using peripheral dual-energy X-ray absorptiometry. Clinical evidence of vitamin D deficiency was noted in 10.8% of the children. Children in the LSES group had a significantly (P < 0.01) lower 25(OH)D concentration (10.4 +/- 0.4 ng/mL) than did those in the USES group (13.7 +/- 0.4 ng/mL). Concentrations of 25(OH)D <9 ng/mL were seen in 35.7% of the children (42.3% in LSES; 27% in USES; P < 0.01). Boys had significantly (P = 0.004) higher 25(OH)D concentrations than did girls. There was a significant negative correlation between the mean serum immunoreactive parathyroid hormone and 25(OH) D concentrations (r = -0.202, P < 0.001). Mean forearm bone mineral density was significantly (P < 0.01) higher in the USES group than in the LSES group. A high prevalence of clinical and biochemical hypovitaminosis D exists in apparently healthy schoolchildren in northern India.

Vitamin D and bone mineral density status of healthy schoolchildren in northern India

Background: Current data on the prevalence of vitamin D deficiency in India are scarce. Objective: We assessed the calcium-vitamin D-parathyroid hormone axis in apparently healthy children from 2 different socioeconomic backgrounds in New Delhi, India. Design: Clinical evaluation for evidence of vitamin D deficiency was carried out in 5137 apparently healthy schoolchildren, aged 10–18 y, attending lower (LSES) and upper (USES) socioeconomic status schools. Serum calcium, inorganic phosphorus, alkaline phosphatase, 25-hydroxyvitamin D [25(OH)D], and immunoreactive parathyroid hormone were measured in 760 children randomly selected from the larger cohort. Bone mineral density of the forearm and the calcaneum was measured in 555 children by using peripheral dual-energy X-ray absorptiometry. Results: Clinical evidence of vitamin D deficiency was noted in 10.8% of the children. Children in the LSES group had a significantly (P < 0.01) lower 25(OH)D concentration (10.4 ± 0.4 ng/mL) than did those in the USES group (13.7 ± 0.4 ng/mL). Concentrations of 25(OH)D <9 ng/mL were seen in 35.7% of the children (42.3% in LSES; 27% in USES; P < 0.01). Boys had significantly (P = 0.004) higher 25(OH)D concentrations than did girls. There was a significant negative correlation between the mean serum immunoreactive parathyroid hormone and 25(OH) D concentrations (r = −0.202, P < 0.001). Mean forearm bone mineral density was significantly (P < 0.01) higher in the USES group than in the LSES group. Conclusion: A high prevalence of clinical and biochemical hypovitaminosis D exists in apparently healthy schoolchildren in northern India.

Bone status in primary hyperparathyroidism assessed by regional bone mineral density from the whole body scan and QUS imaging at calcaneus

To assess the bone mineral density status in primary hyperparathyroidism (PHPT), we studied 64 females with PHPT and 17 healthy women. Regional BMD (arms, trunk, legs) from the whole body scan and conventional sites (lumbar spine, femur, radius) were assessed by DXA. Quantitative ultrasound (QUS) imaging measurements were performed at calcaneus. Sixteen women had history of renal lithiasis, 11 had low impact fracture and 37 women had neither renal lithiasis nor fracture. In the entire group, the mean Z-scores were significantly decreased at all sites (lumbar spine, femur, radius). In all clinical subgroups, the mean Z-scores were significantly decreased at radius. The mean Z-scores in premenopausal women were significantly decreased comparatively to postmenopausal women at lumbar spine and femur. In a group of PHPT females matched to controls for age and BMI, only BMD values at radius were lower in PHPT patients than in control ( P < 0.03). However, from the whole body scan data, all sites but no trunk were significantly involved in PHPT patients ( P < 0.04). Using QUS measurements at calcaneus, the BUA but not SOS in PHPT females was significantly lower ( P = 0.03) than in controls. Our results suggest that low BMD at lumbar spine and femur is encountered preferentially in premenopausal women. The BMD decrease predominates at limbs in PHPT with presumably a gradient from proximal to distal part of the limbs. Indeed, the distal part of the limbs are the most affected areas in PHPT whatever the amount of cortical or trabecular bone.

Statut osseux au cours de l'hyperparathyroïdie primitive mesurée par densité minérale osseuse régionale par densitométrie corps entier et ultrasonographie quantitative au calcanéum

To assess the bone mineral density status in primary hyperparathyroidism (PHPT), we studied 64 females with PHPT and 17 healthy women. Regional BMD (arms, trunk, legs) from the whole body scan and conventional sites (lumbar spine, femur, radius) were assessed by DXA. Quantitative ultrasound (QUS) imaging measurements were performed at calcaneus. Sixteen women had history of renal lithiasis, 11 had low impact fracture and 37 women had neither renal lithiasis nor fracture. In the entire group, the mean Z-scores were significantly decreased at all sites (lumbar spine, femur, radius). In all clinical subgroups, the mean Z-scores were significantly decreased at radius. The mean Z-scores in premenopausal women were significantly decreased comparatively to postmenopausal women at lumbar spine and femur. In a group of PHPT females matched to controls for age and BMI, only BMD values at radius were lower in PHPT patients than in control ( P <0.03). However, from the whole body scan data, all sites but no trunk were significantly involved in PHPT patients ( P <0.04). Using QUS measurements at calcaneus, the BUA but not SOS in PHPT females was significantly lower ( P =0.03) than in controls. Our results suggest that low BMD at lumbar spine and femur is encountered preferentially in premenopausal women. The BMD decrease predominates at limbs in PHPT with presumably a gradient from proximal to distal part of the limbs. Indeed, the distal part of the limbs are the most affected areas in PHPT whatever the amount of cortical or trabecular bone.

Long-term changes in the tibia and radius bone mineral density following spinal cord injury

A prospective inception cohort study with an observational analytic design in a spinal cord injury (SCI) centre hospital. To assess changes in trabecular and compact bone of the tibia and radius prospectively in subjects with SCI. In total, 10 individuals with an acute SCI. Trabecular and compact bone density of the tibia and radius by peripheral quantitative computerised tomography. Analysis of the individual gradients of the curve coefficient showed changes in trabecular bone between -0.19 and -2.46 and in cortical bone between +0.07 and -0.93 in the tibia within 34 months after the SCI. Both trabecular and cortical bone showed a group mean loss of 99 mg/cm(3). No changes were observed in the radius. There is a major decrease in tibia mineral density over 3 years; however, no change is observed for the radius mineral content. Large interindividual differences existed in the patterns of loss in the tibia bone substance after SCI. These patterns indicate that there is no steady state of bone mineral density following 3 years of spinal cord injury.

P0259 BONE MINERAL STATUS IN CHILDREN AGED OVER 3 YEARS UNDERGOING LIVER TRANSPLANTATION

Introduction: Children with chronic liver disease are at risk of reduced bone mineral density (BMD) which may worsen in the months following liver transplantation (OLT). Probable aetiological factors include vitamin D (vit D) malabsorption, immobility and immunosuppressive drugs. Aim: To assess bone mineral health and vit D status in children over 3 years undergoing OLT. Methods: Children with cholestatic liver disease underwent dual energy X-ray absorptiometry (DXA) at the time of listing for OLT and bone mineral density was compared to normative values for children over 3 years. Volumetric bone density (BMAD) was calculated for the lumbar spine to adjust for body size. Bone ions, parathyroid hormone (PTH) and vit D metabolites were also measured. Results: 12 children (6 M; median age 9.4 yrs (3.0 to 14.6 yrs)) underwent assessment at a median of 1.5 months pre OLT. All were ambulant and only 1 previously had fractures. 10 were receiving vit D supplements and 7 supplemental feeding. Median height and weight z-scores were −0.7 (−4.8 to 3.0) and −0.2 (−3.3 to 1.8) respectively. Ionised calcium, phosphate and magnesium were low in 4, 7 and 3 children respectively but no child had a raised serum PTH. Although 9/10 and 5/10 had low 25-OH vit D2 and 25-OH vit D3 respectively, 1,25-(OH)2 vit D was normal in all cases. Median BMD z-score for L2 to L4 lumbar spine was −1.2 (−2.5 to 0.02) and for total body was −1.0 (−1.61 to −0.34). Median BMAD z-score was −0.7 (−3.0 to −1.3). Conclusion: In children aged over 3 undergoing OLT, bone mineral density, vitamin D and PTH status were better than anticipated. Optimal bone health can be achieved in children with chronic liver disease prior to OLT using vitamin D supplementation and ensuring optimal nutrition.

Bone mineral density in females after jejunoileal bypass: a 25-year follow-up study.

Jejunoileal (JI) bypass was a widely performed operation for morbid obesity in the 1970s. The aim of this study was to investigate the long-term status of bone mineral density (BMD) after weight loss induced by this technique. 18 female patients (age 48-79 y, BMI 23-43 kg/m2) had BMD measurements performed 25 years after JI bypass. Dual energy x-ray absorptiometry was used, and measured sites were the lumbar spine L2-L4, left femoral neck and total hip. Vitamin and mineral supplementation had not routinely been prescribed. An assessment was made on age-adjusted BMD values, and as to whether present BMD was related to present demographic and biochemical variables. No significant reduction of BMD was found beyond that which was expected for age. BMD was inversely and separately related to age and body weight. The serum level of vitamin D was low in 45% of the patients, and inversely correlated to body weight and BMI. Alk phosphatase and parathyroid hormone were the best markers for low BMD. These results suggest that JI bypass has not been detrimental to bone density in females. We recommend, however, vitamin D and calcium supplements after malabsorptive procedures for morbid obesity.

Osteoporosis: prevalence in Taiwanese women.

The aim of this study is to understand the current status of bone mineral density (BMD) among Taiwanese women and to determine the relationship between bone mass, weight, height and body mass index (BMI), and the proportion of osteoporosis sufferers, based on World Health Organization standards, in each age group. A total of 4689 women underwent lumbar vertebrae (L2-L4) BMD measurements, and 3529 women underwent femoral neck bone mineral density measurements. BMD was measured using dual-energy X-ray absorptiometry. Standards were based on the BMD of the 20- to 40-year-old age group, as were relationships between height, weight, BMI, and BMD. Pearson correlation revealed a positive relationship between body weight, BMI, and BMD in the femoral neck; other correlations were insignificant. The defined BMD value for a diagnosis of osteoporosis was 0.827 g/cm(2) for lumbar vertebrae and 0.605 g/cm(2) for the femoral neck. The proportion of osteoporosis calculated for each age group in the lumbar vertebrae group was: 40-49 years old, 8.25%; 50-59 years old, 8.62%; 60-69 years old, 14.14%; 70-79 years old, 14.25%; >80 years old, 16.07%. For the femoral neck group, the values were: 40-49 years old, 5.24%; 50-59 years old, 5.28%; 60-69 years old, 11.17%; 70-79 years old, 17.30%; >80 years old, 24%. The total proportion of osteoporosis in the lumbar vertebrae was 10.08%, and in the femoral neck, 7.45%. The BMD of Taiwanese women shows a positive relationship to body weight and BMI in the femoral neck group but not in the lumbar vertebrae group. The proportion of osteoporosis by age group in this cohort was lower than that among Western women.

The relationship between interleukin-1 and its receptor antagonist gene polymorphism and bone mineral density in postmenopausal Korean women

Objective: The objectives were to investigate the relationship between polymorphisms in interleukin-1 (IL-1) and IL-1 receptor antagonist (IL-1ra) gene, and bone mineral density (BMD) in postmenopausal Korean women and to evaluate whether these polymorphisms affect the production of cytokines from whole blood cells.Design: Prospective study.Materials and Methods: IL-1 C511T polymorphism was analyzed by restriction fragment length polymorphism using AvaI after polymerase chain reaction (PCR) and the 86-base pair repeat polymorphism in the IL-1ra gene was examined by PCR and electrophoresis in 202 postmenopausal Korean women. Serum osteocalcin, and CrossLaps (CTX) were measured by immunoassay, and IL-1β and IL-1ra produced by whole blood cells that were cultured for 3 days was measured using enzyme-linked immunosorbent assay. BMD at the lumbar spine and proximal femur were determined by dual energy X-ray absorptiometry.Results: There were no significant differences in BMD of the lumbar spine and proximal femur or serum levels of bone turnover markers across the IL-1 genotypes. Four alleles in IL-1ra gene were identified: A1 (4 repeats), A2 (2 repeats), A3 (5 repeats), and A4 (3 repeats). BMD at the lumbar spine, and proximal femur in women carrying A2 allele, was significantly lower, compared with noncarriage of that allele. Serum osteocalcin levels in the former group were higher than the latter group, but no difference in serum CTX levels between two groups was observed. There were no differences in the distribution of IL-1 genotypes and IL-1ra A2 allele among normal, osteopenic, and osteoporotic postmenopausal women. The production of IL-1β and IL-1ra from whole blood cells was not different according to the IL-1 or IL-1 ra genotypes and the status of BMD.Conclusion: BMD of lumbar spine and proximal femur is associated with a polymorphism in IL-1ra gene in Korean women. Polymorphism of IL-1 and IL-1ra gene does not affect the production of cytokines from whole blood cells. Objective: The objectives were to investigate the relationship between polymorphisms in interleukin-1 (IL-1) and IL-1 receptor antagonist (IL-1ra) gene, and bone mineral density (BMD) in postmenopausal Korean women and to evaluate whether these polymorphisms affect the production of cytokines from whole blood cells. Design: Prospective study. Materials and Methods: IL-1 C511T polymorphism was analyzed by restriction fragment length polymorphism using AvaI after polymerase chain reaction (PCR) and the 86-base pair repeat polymorphism in the IL-1ra gene was examined by PCR and electrophoresis in 202 postmenopausal Korean women. Serum osteocalcin, and CrossLaps (CTX) were measured by immunoassay, and IL-1β and IL-1ra produced by whole blood cells that were cultured for 3 days was measured using enzyme-linked immunosorbent assay. BMD at the lumbar spine and proximal femur were determined by dual energy X-ray absorptiometry. Results: There were no significant differences in BMD of the lumbar spine and proximal femur or serum levels of bone turnover markers across the IL-1 genotypes. Four alleles in IL-1ra gene were identified: A1 (4 repeats), A2 (2 repeats), A3 (5 repeats), and A4 (3 repeats). BMD at the lumbar spine, and proximal femur in women carrying A2 allele, was significantly lower, compared with noncarriage of that allele. Serum osteocalcin levels in the former group were higher than the latter group, but no difference in serum CTX levels between two groups was observed. There were no differences in the distribution of IL-1 genotypes and IL-1ra A2 allele among normal, osteopenic, and osteoporotic postmenopausal women. The production of IL-1β and IL-1ra from whole blood cells was not different according to the IL-1 or IL-1 ra genotypes and the status of BMD. Conclusion: BMD of lumbar spine and proximal femur is associated with a polymorphism in IL-1ra gene in Korean women. Polymorphism of IL-1 and IL-1ra gene does not affect the production of cytokines from whole blood cells.

Bone mineral density in juvenile dermatomyositis: assessment using dual x-ray absorptiometry.

To determine the bone mineral density (BMD) status of our juvenile dermatomyositis (DM) population and to compare the frequency of osteopenia in patients with active disease requiring corticosteroids with that in patients with inactive disease who are not receiving corticosteroids. Medical charts of all children diagnosed as having juvenile DM at our institution between 1989 and 1999 were reviewed for demographic and clinical data, including disease activity and duration of corticosteroid therapy. BMD measurements of the lumbar spine (L1-L4) were performed using dual x-ray absorptiometry (DXA). Z scores were calculated from the BMD data for comparison with published normative data. A total of 15 patients were assessed: 10 with active disease, and 5 with inactive disease who had not taken corticosteroids for an average of 6.0 years (range 3.4-8.1 years). Baseline BMD measurements demonstrated osteopenia or frank osteoporosis in the majority of patients, including 6 of the 10 patients with active disease and 4 of the 5 patients whose disease was in remission. Fourteen patients had serial BMD measurements. Persistent or worsening osteopenia was documented in all patients who had ongoing active disease, except for 3 patients who had been treated with bisphosphonates because of vertebral compression fractures. Osteopenia is common in patients with juvenile DM, and it usually worsens with ongoing disease. It can persist for many years after the disease enters remission. Bisphosphonates appeared to beneficially affect bone mineralization in our patients. Treatment to prevent the long-term complications of osteoporosis in patients with juvenile DM should be considered and requires further study.

Lower serum beta-CrossLaps in male cardiac transplant recipients treated without prednisolone

Post-transplantation bone disease is a frequent problem after successful cardiac transplantation. We performed a cross-sectional analysis of male heart transplant recipients in the late post-transplantation period. Nine patients (group A) had received immunosuppressive therapy with cyclosporin A and mycophenolate mofetil (steroid-free treatment), and 12 patients (group B) remained on triple-drug therapy, which included glucocorticosteroids. Bone mineral density status was analyzed by osteodensitometry and by markers of bone turnover. Osteopenia was common in both groups (44.4% in group A and 50% in group B) as was osteoporosis (30% and 33.3% in groups A and B, respectively). β-CrossLaps were significantly lower in sera of cardiac transplant recipients on double immunosuppressive (i.e., glucocorticosteroid-free) regimen than in sera of patients on triple-drug therapy (428.3, 109.4 vs 661.7, 337.0 pg/ml, P<0.05). Lower serum β-CrossLaps levels in patients undergoing glucocorticosteroid-free treatment may indicate a lower risk of bone deterioration in the long term.

Assessment of bone mineral density in adults and children with Marfan syndrome.

Recent studies indicate that decreased bone mineral density (BMD) occurs in the spine, femoral necks and greater trochanters of some adults and children with Marfan syndrome. Because there is uncertainty regarding the BMD status of patients with Marfan syndrome, we undertook an analysis of BMD in both adults and children with Marfan syndrome. Dual energy X-ray absorptiometry analysis was performed on a convenience sample of 51 patients (30 adults and 21 children) with diagnosed Marfan syndrome from 1993 to 2000. T-Scores (i.e. the number of standard deviations above or below the average normal peak bone density) were determined for comparison of adults. Mean+/-SD of individual BMD values were used for comparison of the data of children. Compared to standard values obtained from normal adult patients, adult males with Marfan syndrome demonstrated significantly reduced femoral neck BMD with an average T-score of -1.54 ( P<0.001), diagnostic of osteopenia. Although osteopenia and osteoporosis were observed in several middle aged and pre- and postmenopausal women, the average T-score value for adult females and children were within normal limits. The etiology and full significance of decreased BMD in adult male patients with Marfan syndrome remain uncertain at the present time. Our results lead us to question the value of aggressive BMD evaluations by DXA in these patients, particularly prior to reaching mid-age. Further investigations will be required to shed insights into the natural history of BMD in adults and children with Marfan syndrome. Any application of bone mineral replacement therapy such as bisphosphonate, selective estrogen receptor modulators, hormone replacement therapy and vitamin D in these patients may be premature based on the existing evidence.

Use of matched historical controls to evaluate the anti-fracture efficacy of once-a-week risedronate

Placebo controls are essential to assess anti-fracture efficacy of new osteoporosis therapies, but inclusion of a placebo arm in a subsequent clinical trial may be limited by practical or ethical considerations; in these cases, use of an historical control may be appropriate. A recent active-controlled study of risedronate 35 mg once a week demonstrated that this regimen produces increases in bone mineral density (BMD) that are comparable to those seen with the risedronate 5 mg daily dose, which has proven anti-fracture efficacy. To assess the anti-fracture efficacy of this new regimen, we have analyzed the fracture data collected in an active controlled study of risedronate dosing regimens (the Once-a-Week study) using matched historical control data from previous placebo-controlled trials. Women in the Once-a-Week study were matched for age, years since menopause, BMD, and prevalent vertebral fracture status, with placebo patients in the Vertebral Efficacy of Risedronate Therapy (VERT) trials forming an historical placebo group. We also constructed an historical active treatment group from the 5 mg daily arm of the VERT trials for comparison with the 5 mg daily and 35 mg once weekly treatment groups in the Once-a-Week study. Data were obtained from the risedronate 5 mg daily group (n=480) and 35 mg once-a-week group (n=485) in the Once-a-Week study and historical control groups representing daily placebo patients (n=114, matched from 993) and risedronate 5 mg daily patients (n=120; matched from 990) in the VERT studies. Patients received calcium supplementation (1000 mg daily); vitamin D was given if baseline serum 25-hydroxyvitamin D levels were low. Over 1 year, new vertebral fracture risk in the 35 mg once-a-week group was reduced by 77% relative to the historical placebo group (1.2% versus 5.0%; RR 0.23; 95% CI, 0.54 to 0.91, P=0.018), similar to the 1-year risk reduction observed in the VERT trials of risedronate 5 mg daily (61-65%). The incidence of new vertebral fractures in the three active treatment groups was similar: 1.7% in the historical risedronate 5 mg group, 1.5% in the risedronate 5 mg daily group from the Once-a-Week study, and 1.2% in the 35 mg once-a-week group. Risedronate 35 mg once a week appears as effective as the 5 mg daily dose in reducing the risk of new vertebral fractures in the first year of treatment. The use of appropriate historical control data provides an approach to the assessment of fracture effects in osteoporosis trials for which placebo-controlled data are not available.

Lower serum beta-CrossLaps in male cardiac transplant recipients treated without prednisolone.

Post-transplantation bone disease is a frequent problem after successful cardiac transplantation. We performed a cross-sectional analysis of male heart transplant recipients in the late post-transplantation period. Nine patients (group A) had received immunosuppressive therapy with cyclosporin A and mycophenolate mofetil (steroid-free treatment), and 12 patients (group B) remained on triple-drug therapy, which included glucocorticosteroids. Bone mineral density status was analyzed by osteodensitometry and by markers of bone turnover. Osteopenia was common in both groups (44.4% in group A and 50% in group B) as was osteoporosis (30% and 33.3% in groups A and B, respectively). beta-CrossLaps were significantly lower in sera of cardiac transplant recipients on double immunosuppressive (i.e., glucocorticosteroid-free) regimen than in sera of patients on triple-drug therapy (428.3+/-109.4 vs 661.7+/-337.0 pg/ml, P<0.05). Lower serum beta-CrossLaps levels in patients undergoing glucocorticosteroid-free treatment may indicate a lower risk of bone deterioration in the long term.

Palangeal quantitative ultrasound, phalangeal morphometric variables, and vertebral fracture discrimination.

The aim of this study was to evaluate the association among phalangeal morphometric parameters, amplitude-dependent speed of sound (AD-SOS), ultrasound bone profile index (UBPI), and spinal bone mineral density (BMD) and fracture status. One hundred women (controls, mean age 53 +/- 12 years) and 40 osteoporotic women (mean age 59 +/- 7 years) with atraumatic fractures, diagnosed by spinal radiographs, were investigated. Quantitative ultrasound (QUS) assessment was performed using the DBM Sonic 1200. Morphological properties of the phalanges were measured from a digitized X-ray image of the hand acquired using industrial film. Spinal BMD was assessed by dual X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). An increase in medullary canal width and a decrease in cortical thickness with aging were observed from the morphometric analysis of the hand radiographs. This phenomenon can be attributed mainly to endosteal resorption. QUS measurements at the phalanges were not significantly related to finger thickness (r <0.20, n.s.). They were significantly correlated to medullary canal ratio (r = -0.57, P <0.0001, for AD-SOS and r = -0.64, P <0.0001, for UBPI) and to cortical thickness (r = +0.52, P <0.0001 for AD-SOS and r = +0.59, P <0.0001 for UBPI). In the discrimination analysis between nonfractured and atraumatic vertebral fracture subjects we found that cortical thickness at the level of the phalanges were similar to lumbar spine BMD. The age and BMI-adjusted odds ratio ranged from 2.0 to 3.1 for QUS, 4.28 for BMD by QCT, 4.1 for BMD by DXA, and 4.1 for cortical thickness. We conclude from these data that phalangeal QUS is related to cortical thickness, which in turn is influenced by endosteal bone resorption occurring in association with spinal osteoporosis.

The association of endogenous hormone concentrations and bone mineral density measures in pre- and perimenopausal women of four ethnic groups: SWAN.

We evaluated bone mineral density (BMD), hormone concentrations and menstrual cycle status to test the hypothesis that greater variations in reproductive hormones and menstrual bleeding patterns in mid-aged women might engender an environment permissive for less bone. We studied 2336 women, aged 42-52 years, from the Study of Women's Health Across the Nation (SWAN) who self-identified as African-American (28.2%), Caucasian (49.9%), Japanese (10.5%) or Chinese (11.4%). Outcome measures were lumbar spine, femoral neck and total hip BMD by dual-energy X-ray densitometry (DXA). Explanatory variables were estradiol, testosterone, sex hormone binding globulin (SHBG) and follicle stimulating hormone (FSH) from serum collected in the early follicular phase of the menstrual cycle or menstrual status [premenopausal (menses in the 3 months prior to study entry without change in regularity) or early perimenopause (menstrual bleeding in the 3 months prior to study entry but some change in the regularity of cycles)]. Total testosterone and estradiol concentrations were indexed to SHBG for the Free Androgen Index (FAI) and the Free Estradiol Index (FEI). Serum logFSH concentrations were inversely correlated with BMD (r = -10 for lumbar spine [95% confidence interval (CI): -0.13, -0.06] and r = -0.08 for femoral neck (95% CI: -0.11, -0.05). Lumbar spine BMD values were approximately 0.5% lower for each successive FSH quartile. There were no significant associations of BMD with serum estradiol, total testosterone, FEI or FAI, respectively, after adjusting for covariates. BMD tended to be lower (p values = 0.009 to 0.06, depending upon the skeletal site) in women classified as perimenopausal versus premenopausal, after adjusting for covariates. Serum FSH but not serum estradiol, testosterone or SHBG were significantly associated with BMD in a multiethnic population of women classified as pre- versus perimenopausal, supporting the hypothesis that alterations in hormone environment are associated with BMD differences prior to the final menstrual period.

Bone mineral density in adolescent female athletes: relationship to exercise type and muscle strength

This study investigated the influence of different exercise types and differences in anatomical distribution of mechanical loading patterns on bone mineral density (BMD) in elite female cyclists, runners, swimmers, triathletes, and controls (N = 15 per group). Associations between leg strength and BMD were also examined. Areal BMD (g x cm(-2)) was assessed by duel-energy x-ray absorptiometry (DXA) (total body (TB), lumbar spine (LS), femoral neck (FN), legs, and arms). Right knee flexion and extension strength was measured using a Cybex Norm isokinetic dynamometer at 60 degrees x s(-1). Runners had significantly higher unadjusted TB, LS, FN, and leg BMD than controls (P < 0.05); higher TB, FN, and leg BMD than swimmers (P < 0.05); and greater leg BMD than cyclists (P < 0.05). Absolute knee extension strength was significantly (P < 0.01) correlated (0.33 < or = r < or = 0.44) with TB, FN, LS, and leg BMD for all groups combined. Weaker but still significant correlations (0.28 < or = r < or = 0.33) existed for normalized (per leg lean tissue mass) knee extension strength and all BMD sites, except FN BMD. There were no significant correlations between absolute or normalized knee flexion strength and any of the BMD variables. Absolute knee extension strength was entered as the second independent predictor for LS and leg BMD in stepwise multiple linear regression analysis (MLRA), accounting for increments of 4% and 12%, respectively, in total explained variation. We conclude that running, a weight bearing exercise, is associated with larger site-specific BMD than swimming or cycling, that the generalized anatomical distribution of loads in triathlon appears not to significantly enhance total body BMD status, and that knee extension strength is only a weak correlate and independent predictor of BMD in adolescent females.

The Lumbar Bone Mineral Density Is Affected by Long-Term Poor Metabolic Control in Adolescents with Type 1 Diabetes mellitus

Aim: To analyze whether bone mineral density (BMD) and bone resorption status are influenced by long-term metabolic control and duration of disease in adolescents with long-standing type 1 diabetes mellitus. Methods: Twenty-seven adolescents (age 13.1 ± 1.7 years, duration of diabetes 6.9 ± 3.0 years) were studied. The BMD, expressed as z score, was measured at the lumbar spine (L1–L4) using dual-energy X-ray absorptiometry, while the urinary excretion of total deoxypiridinoline (Dpyd), a marker of bone resorption, was measured by immunoassay and was corrected by creatinine (Cr). Linear and multivariate correlations between lumbar BMD z score or Dpyd/Cr excretion and age and disease variables [short-term (Hb A_1clatest) or long-term (Hb A_{1cwholeduration}) metabolic control, duration, ‘diabetes impact index’ (mean Hb A_{1cwholeduration} x duration of disease in months)] were sought. Results: In diabetic subjects the mean BMD z score was –0.44 ± (SD) 1.02 (95% CI: –0.03; –0.84), and the Dpyd/Cr excretion was not increased. A negative correlation was found between lumbar BMD z score and age (r –0.59; p = 0.001), duration (r –0.39; p = 0.04), and the diabetes impact index (r –0.4; p = 0.04). The Dpyd/Cr ratio correlated negatively with age (r –0.40; p = 0.04) and positively with height velocity (r 0.42; p = 0.04). By using multiple linear regression, age showed a significant inverse correlation with lumbar BMD z score (β = –0.39; p = 0.0005). A negative correlation was found between lumbar BMD z score and Hb A_{1cwholeduration} (β = –0.40; p = 0.02) or diabetes impact index (β = –0.001; p = 0.01). Conclusions: Poor metabolic control may expose adolescents with long-standing type 1 diabetes to the risk of developing osteopenia in adult age. Optimization of metabolic control in growing diabetic children may prevent osteoporosis in later life.