Calcium and calcitriol prophylaxis attenuates posttransplant bone loss

We performed a prospective, randomized, double-blind study to determine whether calcium and calcitriol prevents posttransplant bone loss. Thirty-eight nondiabetic and 26 diabetic patients without prior steroid exposure undergoing their first kidney or kidney-pancreas transplant were randomized to calcium, calcium plus calcitriol, or placebo. Lumbar spine (LS), femoral neck (FN), and distal radius (DR) bone mineral density scans (BMDs) were obtained at baseline, 6, and 12 months. At 1 year, patients treated with placebo experienced a 2% decline in BMD at the LS and DR and a 1.3% increase at the FN. In contrast, patients treated with calcium and vitamin D had a 0.1% decline at the LS and 2.9% and 4.8% increases at the DR and FN, respectively. Patients receiving cyclosporine had more bone loss than those receiving tacrolimus. Our results demonstrate a small therapeutic effect of calcium and calcitriol and suggest that tacrolimus is less osteotoxic than cyclosporine.     

Calcitriol does not prevent bone loss in patients with asthma receiving corticosteroid therapy: a double-blind placebo-controlled trial

Introduction Oral glucocorticoid therapy reduces bone mineral density (BMD) and increases fracture risk. It is uncertain whether inhaled glucocorticoids, the most commonly used long-term therapy for asthma, have a similar effect. If bone loss does occur, it is unclear whether this is preventable by calcitriol. Patients with asthma receiving inhalational plus intermittent oral glucocorticoids lose bone, and treatment with 0.5 μg/day of calcitriol will prevent bone loss.Methods A 2-year randomized double-blind placebo-controlled trial. One hundred eight patients with asthma were stratified by gender, age, and inhaled glucocorticoid dose and treated with calcitriol (n=55) or placebo (n=53). There were 41 men (mean age 53.2±1.7 years) and 67 women (mean age 49.1±1 years) with moderate to severe asthma (requiring ≥800 μg/day of beclomethasone dipropionate or equivalent maintenance therapy). BMD values at the lumbar spine (LS) and femoral neck (FN) were measured at baseline and at 6, 12, and 24 months using dual x-ray absorptiometry.Results Changes in LS and FN BMD. Bone loss occurred in both groups at the FN (both p<0.03) and at the LS in the calcitriol (p<0.001), but not the control, group. Bone loss was not less in the calcitriol group at either site.Conclusion Patients with asthma receiving inhalational plus intermittent short courses of oral glucocorticoids lose bone. Calcitriol is unlikely to be appropriate therapy against this bone loss.     

Bone Mass and Markers of Bone and Calcium Metabolism in Postmenopausal Women Treated with 1,25-Dihydroxyvitamin D (Calcitriol) for Four Years

To evaluate the long-term effect of calcitriol treatment on bone mineral density (BMD) of the femoral neck and lumbar spine and the parameters of calcium and bone metabolism in elderly women, 55 healthy, postmenopausal women, all aged 66 years, were enrolled in the study. Eighteen started a 4-year supplementation with 0.5 μg of calcitriol daily and 37 served as controls. Calcium intake of all the subjects was adjusted to 800 mg daily. In 4 years femoral neck BMD increased by 3.0% in the calcitriol group, but decreased by 1.6% in the control group (P= 0.009). The respective changes in lumbar spine BMD were +2.3% and +0.9% (P= 0.067). Two years' treatment with calcitriol increased the intestinal absorption of strontium by 57% (P < 0.001), doubled the urinary excretion of calcium (P < 0.001), and decreased the mean parathyroid hormone (PTH) level by 32% (P < 0.01). In the calcitriol group the marker of bone formation, serum osteocalcin, decreased by 27% (P < 0.01), and the marker of bone resorption, serum C-telopeptide of type I collagen (CTx), by 33% (P= 0.05) after 2 years. In two subjects the calcitriol dose had to be reduced because of hypercalciuria. We conclude that calcitriol treatment increases bone mass at the femoral neck and lumbar spine, the increases being maintained for up to 4 years. The gain in bone mass results from reduced bone turnover which is partly a consequence of the enhanced intestinal absorption of calcium and suppressed serum PTH levels. Received: 8 January 1999 / Accepted: 29 February 2000     

Bone mineral density and osteoporosis among a predominantly Caucasian elderly population in the city of São Paulo, Brazil

This cross-sectional study covered 301 individuals over 70 years of age—207 women (W) and 94 men (M)—living in the city of São Paulo, Brazil. Our aims were to evaluate the prevalence of low bone mineral density (BMD) in this population and the possible factors that influence BMD. The subjects were submitted to a bone densitometry scan (DXA) to evaluate the BMD at lumbar spine (LS), femoral neck (FN), trochanter (T), total femur (TF) and total body composition. At the time, the participants filled in a questionnaire about lifestyle habits, diet and medical history, as well as having blood samples taken to check hormone and biochemical levels. Anthropometric parameters were measured. Osteopenia and osteoporosis were defined in accordance with the criteria suggested by the World Health Organization. In the different sites studied, the prevalence of osteopenia and osteoporosis varied, in men ranging 33.3–57.4% and 6.4–16.1%, respectively, and in women ranging 36.6–56.5% and 22.2–33.2%, respectively. Weight was the variable that most strongly correlated with BMD at the proximal femur in both sexes (men, r =0.44–0.52; women, r =0.48–0.52) and with BMD at LS in women ( r =0.44). Height was the parameter that best correlated with BMD at LS in men ( r =0.34). In men follicle-stimulating hormone, growth hormone and glycemia correlated with BMD at T and TF, while plasma albumin only correlated with BMD at T. In women glycemia correlated with BMD at LS, and follicle-stimulating hormone correlated with BMD at FN, T and TF. In conclusion, we found a high prevalence of osteopenia and osteoporosis in this population, with weight being the best predictor of BMD. The prevalence of osteoporosis and osteopenia at FN was as high in men as that observed in women.     

Differential action of pamidronate on trabecular and cortical bone in women with involutional osteoporosis

Since osteoporotic fractures are mainly related to the diminution of the bone mineral density (BMD), the effect of pamidronate (3-amino-1-hydroxy-propylidene) 1,1-bisphosphonate on the BMD of the spine, proximal femur and radius shaft was evaluated in an initial cohort of 35 postmenopausal women with at least one vertebral fracture due to involutional osteoporosis.Pamidronate was given continuously during 18 months in a daily oral dose of 4.8 to 6.0 mg/kg supplemented with calcium (1 g/day).BMD — measured by dual photon absorptiometry — increased after one year 5.3±1.0% (P<0.001) in lumbar spine and 5.3±1.5% (P<0.001) over trochanter. However no significant changes were observed in the BMD of the femoral neck, Ward's triangle or in the cortical bone of the radius shaft measured by single photon absorptiometry.Pamidronate also decreased significantly urinary hydroxyproline-creatinine excretion after 6 months and thereafter maintained a plateau. After 18 months of treatment the diminution was 42.6±4.9% (P<0.001).The differing effects of pamidronate on the BMD of lumbar spine and proximal femur might be ascribed to dissimilarities between the proportions of trabecular and cortical bone in these. These results suggest that pamidronate may be prescribed to prevent fractures in cases of involutional osteoporosis with a significant decrease of BMD in lumbar spine and/or trochanter.     

Correlation of vitamin D,bone mineral density and parathyroid hormone levels in adults with low bone density

Background:

Bone mineral densiy (BMD) is known to be affected by serum 25-hydroxyvitamin D (25(OH) D) levels, intact parathyroid hormone (iPTH) levels. Indian data pertinent to above observation is scant. Our study aimed to investigate the relationships between serum 25-hydroxyvitamin D (25(OH) D) levels, intact parathyroid hormone (iPTH) levels and bone mineral density (BMD) in a cohort of Indian patients.

Materials and Methods:

Adults with or without fragility fractures with low BMD at the hip or lumbar spine were evaluated clinically along with laboratory investigations. T-scores of the hip and spine were derived from BMD-DEXA (dual-energy X-ray absorptiometry). Multivariate regression models were used to investigate the relationships between serum 25(OH) D, iPTH and BMD.

Results:

Total of 102 patients (male:female = 38:64) with a mean age of 62.5 ± 6.4 years were included in the study. Forty-four patients had osteopenia. Osteoporosis was present in 58 patients. The mean values for serum 25(OH) D and iPTH levels were 21.3 ± 0.5 ng/ml and 53.1 ± 22.3 pg/ml, respectively. In 84.3% of patients, serum 25(OH) D levels were below 30 ng/ml (Normal = 30-74 ng/ml), confirming vitamin D deficiency. There was no association between 25(OH) D levels and BMD at the hip or lumbar spine (P = 0.473 and 0.353, respectively). Both at the hip and lumbar spine; iPTH levels, male gender, body mass index (BMI) and age were found to be significant predictors of BMD. Patients with higher BMI had significantly lower BMD and T-score. At levels <30 ng/ml, 25(OH) D was negatively associated with iPTH (P = 0.041).

Conclusion:

Among our cohort of patients with low BMD, no direct relationship between serum 25(OH) D levels and BMD was observed. However, a negative correlation between iPTH and 25(OH) D at serum 25(OH) D concentrations <30 ng/ml. Serum iPTH levels showed a significant negative association with BMD at the hip and lumbar spine. Our findings underscore the critical role of parathyroid hormone in bone metabolism and health.     

Bone mineral density in Norwegian premenopausal women

The aims of this study were: 1) to determine bone mineral density (BMD) in different age groups, 2) to determine the prevalence of low BMD, and 3) to determine the possible association between BMD and a number of risk factors in Norwegian premenopausal women. BMD of the lumbar spine (L₂–L₄), total body, and the hip (total femur, femur neck, and trochanter) were measured using dual-energy X-ray absorptiometry (Prodigy, Lunar) in 145 randomly selected women aged 13–39 years. Information on other factors thought to influence BMD was obtained through questionnaire and a clinical interview. The group aged 25–29 years had the highest mean BMD in the total body, lumbar spine, and total femur while the group aged 13–19 years had the highest mean BMD in the femur neck and the trochanter. The mean BMD values of Norwegian premenopausal women were 3.4–5.1% higher than US/European reference data (P<0.05). Five percent of the study sample aged 20–39 years were defined with low BMD (Z-score <–2) using the standard values from this study. Weight-bearing physical activity, body weight, body height, and age were positively associated with BMD, whilst menstrual dysfunction and previous pregnancy were associated with lower BMD in some of the measurement sites. The results show that the factors associated with BMD are extensive, and the strategies to prevent low BMD have to be multifactorial. A follow-up study should be conducted on the study sample to investigate actual mean BMD values and BMD changes through time.     

High parity is associated with increased bone size and strength

Some, but not all, studies report an association between decreased hip fracture risk and high parity despite similar bone mineral density (BMD). Our hypothesis was that bone size, a major determinant of bone strength, is greater in women with high parity compared with low parity or nulliparous women. A cross-sectional study of 168 Hutterite women aged 40–80 years was conducted. BMD, bone mineral content (BMC) and bone area of the total body (TB), hip, femoral neck (FN), and lumbar spine (LS) were measured, as well as bone geometry at the 4% and 20% distal radius and bending strength at 20% radius. Diet and activity recall and strength measurements were obtained. Of the 168 women, 42 (25%) were nulliparous while the remaining women reported 1 to 16 births (median=6). Of the 126 parous women, 122 (97%) breast-fed their infants (range 1.5–24 months). Hip, FN and LS BMD were not associated with either parity or months of breast-feeding. TB BMC and bone area (both, p <0.05) and FN bone area ( p <0.01) were associated with parity. FN bone area was 4% greater in women with 7+ vs 1–4 children. Torsional bending strength, which includes structural and material bone properties, at the 20% distal radius was greater with higher parity ( p =0.01). No bone measure was associated with average months of breast-feeding. High parity is associated with increased radial torsional bending strength and femoral neck size. The greater femoral neck size, without higher BMD, may explain the reduced hip fracture risk among women with high parity previously reported in some studies.     

Risk factors for osteoporosis after renal transplantation and effect of vitamin D receptor Bsm I polymorphism

Objective

Rapid loss of vertebral or hip mineral density after renal transplantation is a major complication which occurs within 6-12 months. The aim of this study was to evaluate risk factors contributing to bone disease in the early stage after renal transplantation and the effect of vitamin D receptor (VDR) gene polymorphisms.

Methods

We prospectively followed for up to 12 months 44 patients (29 men and 15 women) with end-stage renal disease who underwent kidney transplantation. All patients received prednisone with either cyclosporine (CsA)/mycophenolate mofetil (MMF) or tacrolimus (Tac)/MMF therapy. Spine, hip, and whole body bone mineral density (BMD) was measured at 12 months after transplantation. According to World Health Organization recommendations, our patients were categorized as normal, osteopenic, or osteoporotic BMD levels. VDR alleles were genotyped as BB, Bb, or bb by polymerase chain reactions based on polymorphism at the Bsm I restriction site.

Results

Forty-six percent of patients were normal, 43% osteopenic, and 11% osteoporotic. Significant risk factors for osteoporosis among renal transplant recipients were younger age and pretransplant high intact parathyroid hormone (iPTH) levels. (P values .045 and .027, respectively). According to polymorphic group categorization, posttransplant serum Ca was significantly higher in patients with BB or Bb genotype than in those with bb genotype (P = .012). Although there was no statistical significance regarding iPTH levels, it was higher among Bb+BB than the bb genotype group. Also, first-year BMD analysis after transplantation according to Bsm I polymorphism showed significant differences in femur BMD levels according to the dual classification of polymorphism (P < .05). The BMD levels in the bb group was higher than in the Bb+BB group.

Conclusions

Although high pretransplant iPTH levels and younger age enhanced posttransplant bone loss, functionally different alleles of the VDR gene may modulate bone turnover during the first year after renal transplantation.     

Sodium monofluorophosphate increases vertebral bone mineral density in patients with corticosteroid-induced osteoporosis

Corticosteroid-induced osteoporosis, which particularly affects the axial skeleton and the proximal femur, is characterized by a state of low bone remodelling. Fluoride is a potent stimulator of trabecular bone formation which could potentially be useful in the treatment of corticosteroid-induced osteoporosis. We investigated the effects of sodium monofluorophosphate (26 mg/day of fluoride) combined with 1000 mg of calcium (MFP-calcium-treated group), or of calcium alone (control), given for 18 months, on bone mineral density (BMD) of lumbar spine (LS), femoral neck (FN) and midfemoral shaft (FS) in 48 patients with corticosteroid-induced osteoporosis. Mean ages were 49.4±3.1 and 51.6±3.0 years (mean± SEM), duration of corticosteroid therapy 7.5±1.8 and 9.3±1.7 years, and mean daily dose of prednisone 18.2±2.3 and 12.1±1.1 mg in the MFP-calcium-treated group and controls, respectively. Initial BMDs (expressed as theZ-score, i.e. the difference in standard deviations from age- and sex-matched normal subjects) were –1.5±0.2 and –1.2±0.2 for LS, –1.4± 0.2 and –1.3±0.2 for FN, and –0.8±0.3 and –0.6±0.3 for FS, in the MFP-calcium-treated group and controls, respectively. Analysis by linear regression of 6-monthly measurement values revealed BMD changes of +7.8 ±2.2 versus + 3.6±1.3% (p<0.02) for LS, –1.5±1.8 versus +0.9 ±1.8% for FN, and –1.1±1.1 versus –0.5±1.4% for FS after 18 months of follow-up in the MFP-calcium-treated group and controls, respectively. For comparison, 17 patients with idiopathic osteoporosis (mean age 63.9±2.0 years), with initial BMDs of –1.3±0.4, –1.6±0.3 and –0.8±0.4 (Z-score for LS, FN and FS, respectively), received MFP and calcium for 22.1±1.7 months. BMD changes in idiopathic osteoporosis were +9.3±2.7% (p<0.005), –1.3±2.0% and +0.6± 0.9% for LS, FN and FS, respectively. These results indicate that the combination sodium monofluorophosphate and calcium was more efficient than calcium alone in increasing lumbar spine BMD in patients with corticosteroid-induced osteoporosis; neither femoral neck nor femoral shaft BMD was affected. Moreover, these effects were similar in patients with corticosteroid-induced and idiopathic osteoporosis.     

Home-based resistance training improves femoral bone mineral density in women on hormone therapy

This study tested whether moderate resistance training would improve femoral bone mineral density (BMD) in long-term users of hormone therapy with low BMD. The study was a 2-year randomized, controlled, trial (RCT) of moderate resistance training of either the lower extremity or the upper extremity. Eighty-five women participated in a 6-month observation period. The setting was center-based and home-based training. The participants were 189 women aged 59–78 years, with total femur T-scores from –0.8 to –2.8 and on hormone therapy (HT) for a minimum of 2 years (mean 11.8 years); 153 completed the trial. Lower extremity training used weight belts (mean 7.8 kg) in step-ups and chair rises; upper extremity training used elastic bands and dumbbells. Measurements were BMD and body composition [dual-energy X-ray absorptiometry (DXA)], bone turnover markers. Total femoral BMD showed a downward trend during the observation period: 0.35%±0.18% (P=0.14). The response to training was similar in the upper and lower groups in the primary outcomes. At 2 years, total femoral BMD increased 1.5% (95% CI 0.8%–2.2%) in the lower group and 1.8% (95% CI 1.1%–2.5%) in the upper group. Trochanter BMD increased 2.4% (95% CI 1.3%–3.5%) in the lower group and 2.5% (95% CI 1.4%–3.6%) in the upper group (for both analyses time effect P<0.001). At 1 year, a bone resorption marker (C-telopeptide) decreased 9% (P=0.04). Bone formation markers, bone-specific alkaline phosphatase, decreased 5% (P<0.001), and N-terminal type I procollagen peptide decreased 7% (P=0.01). Body composition (percent lean and percent body fat) was maintained in both groups. We concluded that long-term moderate resistance training reversed bone loss, decreased bone turnover, increased femur BMD, and maintained body composition. The similarity of response in upper and lower groups supports a systemic response rather than a site-specific response to moderate resistance training.     

Treatment of hyperparathyroidism with cinacalcet in kidney transplant recipients

Background

After successful kidney transplantation, hyperparathyroidism can persist in 10%–50% of patients and can harmfully affect bone metabolism. Calcimimetic cinacalcet is a new treatment option in the management of persistent hyperparathyroidism in these patients.

Methods

This prospective, clinical study of 11 patients included those who had a serum intact parathyroid hormone (iPTH) concentration >65 ng/L, a serum creatinine concentration was <200 μmol/L, stable kidney graft function, and were >1 year since transplantation. Patients were not treated with drugs other than calcitriol that could influence bone metabolism. During the 6-month observation period, in which the stability of measured parameters was determined, and in the 12-month treatment period (cinacalcet 30 mg/d), we followed serum concentrations of calcium, phosphate, iPTH, creatinine, vitamin 25OH D₃, bone-specific alkaline phosphatase (ALP), osteocalcin, collagen degradation fragments (CTX), urinary calcium excretion, and bone mineral density (BMD).

Results

During the treatment period, the serum calcium concentration decreased significantly (from 2.50 ± 0.12 to 2.32 ± 0.12 mmol/L; P < .01). Serum iPTH concentration decreased significantly (from 247 [range, 199–362] at time 0 to 198 [range, 165–233] ng/L after 1 month of treatment; P < .05), but increased slightly thereafter. After 6 months of treatment, the serum concentration of ALP and CTX increased significantly, but decreased thereafter. There were no significant changes in the other parameters assessed. Renal function remained stable during the treatment period. The BMD of the lumbar spine, hip, and forearm did not change during the 12 months of treatment.

Conclusion

Cinacalcet was effective in treating posttransplant hyperparathyroidism, resulting in decreased calcemia and transient decreased iPTH. ALP and CTX transiently increased during therapy, but other markers of bone metabolism remained unchanged. Twelve months of cinacalcet treatment did not result in a change in BMD. Cinacalcet seems to be a safe drug with no negative effect on renal function.     

Bone mineral density and parathyroid function in patients on maintenance hemodialysis

Background

The relationship between parathyroid function, an important determinant of bone turnover, and bone mineral density (BMD) in patients with chronic kidney disease is not fully understood. We wanted to analyze the association between BMD and parathyroid function in hemodialysis patients in details.

Methods

In a cross-sectional design, data from 270 patients (age 55 ± 15 years, 60% men, all Caucasian) on maintenance hemodialysis were analyzed. All patients underwent dual energy X-ray absorptiometry of the lumbar spine (LS), femoral neck (FN) and distal radius (DR). In addition to routine laboratory tests, blood samples were collected for iPTH, serum markers of bone metabolism (alkaline phosphatase, type I collagen crosslinked-C-telopeptide) and 25OH vitamin D.

Results

Based on Z-scores, bone mineral density was moderately reduced only at the femoral neck in the total cohort. The average Z-score of the ??low PTH?? group (iPTH < 100 pg/ml) was not different from the Z-score of patients with iPTH in the ??target range?? (100?C300 pg/ml) at any measurement site. While iPTH was negatively correlated with BMD at all measurement sites in patients with iPTH > 100 pg/ml (rho = ?0.255, ?0.278 and ?0.251 for LS, FN and DR, respectively, P < 0.001 for all), BMD was independent of iPTH in patients with iPTH < 100 pg/ml. Furthermore, iPTH was not associated with serum markers of bone metabolism, but these markers were negatively correlated with BMD in the ??low PTH?? group.

Conclusions

Low PTH levels are not associated with low BMD in patients with end-stage kidney disease. Furthermore, bone metabolism seems to be independent of iPTH in patients with relative hypoparathyroidism likely reflecting skeletal resistance to PTH.     

Bone gained from physical activity and lost through detraining: a longitudinal study in young males

The aim of this study was to investigate the effect of training and detraining on bone mineral density of both weight-bearing and non-weight-bearing bone in a cohort of young males who participated in ice hockey training. Forty-three healthy adolescent ice hockey players (16.7±0.6 years) training for a mean of 9.7±2.4 h/week and 25 control subjects (16.8±0.3 years) training for 2.1±2.7 h/week, were included in this longitudinal study. Bone mineral density (BMD, g/cm²) of the arms, the dominant and non-dominant humerus, dominant and non-dominant femur, and the right femoral neck, total hip, and bone area of the femur, humerus and hip were measured at baseline and again after 30 and 70 months using dual-energy X-ray absorptiometry. From baseline to the first follow-up, athletes gained significantly more BMD in the femoral neck (0.07 versus 0.03 g/cm²) and arms (0.09 versus 0.06 g/cm²) compared with the controls (P=0.04 for both). Between the first and the second follow-up, 21 ice hockey players stopped their active sports career. These men lost significantly more BMD at the femoral neck (–0.02 versus –0.10 g/cm², P<0.001), total hip (–0.05 versus –0.09, P=0.04), dominant (0.02 versus –0.03 g/cm², P=0.009) and non-dominant humerus (0.03 versus –0.01 g/cm², P=0.03) than the still active ice hockey players (n=22). At the second follow-up examination, at 22 years of age, the former ice hockey players still had significantly higher BMD at the non-dominant humerus than the controls (P<0.01). During the total study period, the still active athletes (n=22) gained significantly more BMD compared with the controls at the femoral neck (0.09 g/cm²; P=0.008), total hip (0.05 g/cm², P=0.04) and arms (0.07 g/cm²; P=0.01). No differences were seen in bone areas when comparing the different groups. In conclusion, training associated with ice hockey is related to continuous accumulation of BMD after puberty in males. Reduced activity is followed by BMD loss within 3 years of cessation of sports career at predominantly weight-bearing sites. The effects are confined to bone density and not bone size.     

Preferential low bone mineral density of the femoral neck in patients with a recent fracture of the proximal femur

Bone mass is an important determinant of resistance to fractures. Whether bone mineral density (BMD) in subjects with a fracture of the proximal femur (hip fracture) is different from that of age-matched controls is still debated. We measured BMD of the femoral neck (FN) on the opposite side to the fracture, as well as femoral shaft (FS) and lumbar spine (LS) BMD by dual-photon absorptiometry in 68 patients (57 women and 11 men, mean age 78.8±1.0) 12.4±0.8 days after hip fracture following a moderate trauma. These values were compared with BMD of 93 non-fractured elderly control subjects (82 women and 11 men), measured during the same period. As compared with the controls, FN BMD was significantly lower in fractured women (0.592±0.013 v. 0.728±0.014 g/cm²,P<0.001) and in fractured men (0.697±0.029 v. 0.840±0.052,P<0.05). Expressed as standard deviations above or below the mean BMD of age and sex-matched normal subjects (Z-score), the difference in FN BMD between fractured women and controls was highly significant (–0.6±0.1 v. +0.1±0.1,P<0.001). As compared with mean BMD of young normal subjects, BMD was decreased by 36.9±1.4 and 22.4±1.5% (P<0.001) in fractured and control women, respectively. There was no significant difference between FN BMD of 33 women with cervical and 24 with trochanteric hip fractures (0.603±0.017 v. 0.577±0.020). FN BMD was lower than 0.705 g/cm² in 90% of fractured women. The prevalence of fracture increased with decreasing FN BMD, reaching 100% with values below 0.500 g/cm². FS and LS BMD were significantly lower in women with hip fracture than in controls (1.388±0.036 v. 1.580±0.030,P<0.001, for FS, and 0.886±0.027 v. 0.985±0.023,P<0.01, for LS), but these differences were not significant when expressed as a Z-score. In men with a recent hip fracture, FS BMD was significantly lower than in controls (1.729±0.096 v. 2.069±0.062,P<0.01), but the difference at the LS level did not reach statistical significance. These results indicate that both women and men with a recent hip fracture had decreased bone mineral density of the femoral neck, femoral shaft and lumbar spine. However, the difference appeared to be of higher magnitude for the femoral neck suggesting a preferential bone loss at this site.     

The effect of 1-year transdermal estrogen replacement therapy on bone mineral density and biochemical markers of bone turnover in osteopenic postmenopausal systemic lupus erythematosus patients: a randomized,double-blind,placebo-controlled trial

We studied the effect of 1-year transdermal estrogen replacement therapy (ERT) on bone mineral density (BMD) and biochemical markers of bone turnover in osteopenic postmenopausal systemic lupus erythematosus (SLE) patients in a randomized, double-blind, placebo-controlled trial. SLE patients were randomly allocated to treatment (estradiol; 50 g transdermal 17-estradiol; n=15) or placebo (n=17) group. Both groups received 5 mg continuous oral medroxyprogesterone acetate, 500 mg calcium and 400 IU vitamin D₃. L₁–L₄ spine (LS), left femur and total hip BMD were measured at baseline and at 6 and 12 months. Serum osteocalcin (OC) and degradation products of C-terminal telopeptides of type-I collagen (CTx) levels were measured at baseline and 3, 6, 9, and 12 months. There was a significant difference in the percentage change of LS BMD at 6 months between the two groups (103.24±3.74% (estradiol group) vs 98.99±3.11% (placebo group); P<0.005). There was a significant decrease within the estradiol group in the CTx levels between baseline and all subsequent visits (P<0.05). There was no significant difference in SLE disease activity index, Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) damage index and corticosteroid dose during the study period. Transdermal estradiol may prevent bone loss in postmenopausal SLE women at the lumbar spine and femur, with no increase in disease activity among postmenopausal SLE women receiving transdermal ERT. The high dropout rate (8/15) leads us to the conclusion that efficacy of HRT in a high-risk group such as SLE women can be attained only in a small number of patients, provided all inclusion/exclusion criteria are strictly adhered to.     

Effects of a combined alendronate and calcitriol agent (Maxmarvil®) on bone metabolism in Korean postmenopausal women: a multicenter, double-blind, randomized, placebo-controlled study

Introduction A randomized, double-blind, prospective, 24-week clinical trial was performed to evaluate the effects of a combinative agent, Maxmarvil, of calcitriol (0.5 μg) and alendronate (5 mg) on bone metabolism in postmenopausal women.Methods A total of 217 postmenopausal women with osteoporosis were enrolled; 199 patients were randomly assigned to one of two treatment groups (Maxmarvil group or alfacalcidol group). None of the patients were vitamin-D-deficient, as assessed by serum 25-hydroxyvitamin D (25(OH)D), nor had they received any drugs affecting bone metabolism before enrollment. Bone mineral densities (BMD) of L1–L4 and the femur were measured by dual-energy X-ray absorptiometry (DXA) at the initial assessment and after 6 months of treatment. Serum biochemical assays, including serum calcium, 24-h urinary calcium excretion, and bone turnover markers (both bone-specific alkaline phosphatase [bsALP] and urine N-telopeptide [NTx]), were performed at the baseline and after 3 and 6 months of treatment.Results In the Maxmarvil group, the BMD of the lumbar spine increased up to 2.42±0.5% from the baseline after 6 months (p<0.05). On the other hand, the change in BMD in the alfacalcidol group was 0.28±0.5% after 6 months. There was no significant difference in femoral BMD between the two groups. The levels of bsALP and NTx were significantly lower in the Maxmarvil group than in the alfacalcidol group (−22.04±3.9% vs. −11.42±2.8% [p<0.05] and −25.46±5.2% vs. 1.24±6.2% [p<0.001], respectively). Interestingly, there was a significantly smaller amount of 24-h urinary calcium in the Maxmarvil group (p<0.05).Conclusions Our study demonstrates that a combination of calcitriol and alendronate is quite effective in preventing bone loss, with the advantage of lesser hypercalciuric effect of calcitriol in the postmenopausal osteoporotic women.     

The Impact of Intense Training on Endogenous Estrogen and Progesterone Concentrations and Bone Mineral Acquisition in Adolescent Rowers

The effect of 18 months of training on the ovarian hormone concentrations and bone mineral density (BMD) accrual was assessed longitudinally in 14 adolescent rowers and 10 matched controls, aged 14–15 years. Ovarian hormone levels were assessed by urinary estrone glucuronide (E₁G) and pregnanediol glucuronide (PdG) excretion rates, classifying the menstrual cycles as ovulatory or anovulatory. Total body (TB), total proximal femur (PF), femoral neck (FN) and lumbar spine (LS) (L2–4) bone mass were measured at baseline and 18 months using dual-energy X-ray densitometry. Results were expressed as bone mineral content (BMC), BMD and bone mineral apparent density (BMAD). Five rowers had anovulatory menstrual cycles compared with zero prevalence for the control subjects. Baseline TB BMD was significantly higher in the ovulatory rowers, with PF BMD, FN BMD and LS BMD similar for all groups. At completion, the LS bone accrual of the ovulatory rowers was significantly greater (BMC 8.1%, BMD 6.2%, BMAD 6.2%) than that of the anovulatory rowers (BMC 1.1%, BMD 3.9%, BMAD 1.6%) and ovulatory controls (BMC 0.5%, BMD 1.1%, BMAD 1.1%). No difference in TB, PF or FN bone accrual was observed among groups. This study demonstrated an osteogenic response to mechanical loading, with the rowers accruing greater bone mass than the controls at the lumbar spine. However, the exercise-induced osteogenic benefits were less when rowing training was associated with low estrogen and progesterone metabolite excretion. Received: 8 December 1998 / Accepted: 15 March 1999     

Beneficial Effect of Copper Supplementation on Deposition of Fluoride in Bone in Fluoride- and Molybdenum-Fed Rabbits

Fluorosis is a major public health problem in the world, including India. The present study was undertaken to investigate the role of molybdenum (Mo) in the deposition of fluoride (F) in bone and whether copper (Cu) supplementation has any alleviating role when F and Mo are ingested together. For this purpose, four groups of rabbits were used [control (C), fluoride (F), fluoride + molybdenum (F + Mo), and fluoride + molybdenum + copper (F + Mo + Cu)] to find out the effect of these treatments on various bone-related parameters like intact parathyroid hormone (iPTH), alkaline phosphatase and Cu in serum, hydroxyproline and calcium (Ca) in urine, and minerals (F, Cu, manganese, and zinc) in femur bone ash. Bone mineral content (BMC), bone mineral density (BMD) [by dual energy X-ray absorptiometry (DXA)], and strength of femur bones were also assessed. F content in the femur was significantly higher (P < 0.01) in all experimental groups compared to control group. Mo supplementation increased F deposition in femur bone in the F + Mo group, whereas supplementation of Cu reduced F deposition in the F + Mo + Cu group compared to the F + Mo and F groups. Levels of Cu in femurs of the F + Mo and F + Mo + Cu groups were significantly higher (P < 0.05, P < 0.01, respectively) than in the C group, although serum Cu was significantly lower in the F and F + Mo than the C and F + Mo + Cu groups. Magnesium levels in the F + Mo group were significantly higher (P < 0.05) than in the F and F + Mo + Cu groups. Cu supplementation in the F + Mo + Cu group increased deposition of zinc significantly (P < 0.05) compared to the F and F + Mo groups. Serum iPTH, alkaline phosphatase, and urinary hydroxyproline and Ca were significantly higher (P < 0.01) in the F and F + Mo than in the C and F + Mo + Cu groups. However, serum iPTH and urinary hydroxyproline were higher in the F + Mo group than the F group. Alkaline phosphatase was significantly higher in the F + Mo group than the F and F + Mo + Cu groups. Levels of serum Cu in the F and F + Mo groups were lower than in the C group, though serum Cu was significantly higher in the F + Mo + Cu than in all other groups. DXA analysis of femur bone indicated that BMD in the F + Mo group was significantly higher than in the F (P < 0.05), C (P < 0.01), and F + Mo + Cu (P < 0.05) groups. However, there was no significant difference in BMC among the groups. Bone strength was significantly higher (P < 0.05) in the F + Mo group than in the C group. Results of the present study show that ingestion of Mo with F does not create secondary Cu deficiency (due to increased excretion of Cu through urine). However, Cu concentration was decreased in serum in this group (F + Mo) compared to the C and F + Mo + Cu groups. Deposition of F in femur bone was more (22%) when it was given along with Mo compared to F alone, while F deposition in femur bone was less in the F + Mo + Cu group by 80% compared to the F group. Also, deposition of F in the F + Mo + Cu group was 120% less compared to the F + Mo group. The increase in F level due to Mo addition appears to be offset by supplementation with Cu. Supplementation with Cu showed a beneficial effect on bone resorption as well as bone formation.     

Effects of alendronate on bone mineral density and bone metabolic markers in patients with liver transplantation

Introduction The purpose of this study was to evaluate the effects of alendronate (ALN) on bone mineral density (BMD) and bone turnover markers in patients with orthotopic liver transplantation (OLT). Methods In the prospective, controlled, open study with 24 months of follow-up, 98 patients with OLT were randomised to receive ALN 70 mg weekly or no ALN; calcium (Ca) 1,000 mg daily and 0.5 mcg calcitriol daily were provided to all patients. Lumbar spine (LS) and hip BMDs were measured at 6-month intervals by dual-energy X-ray absorptiometry (DEXA). Spinal radiographs were obtained to assess vertebral fractures. Additionally, bone turnover markers, serum parathyroid hormone (PTH) and biochemical parameters were determined every 3 months. Results Compared with the control group, the ALN group showed significant increases in BMD of the LS (5.1±3.9% vs 0.4±4.2%, p<0.05 at 12 months, 8.9±5.7% vs 1.4±4.9%, p<0.05 at 24 months), femoral neck (4.3±3.8% vs −1.1±3.1%, p<0.05 at 12 months, 8.7±4.8% vs 0.6±4.5%, p<0.05 at 24 months) and total femur (3.6±3.8% vs −0.6±4.0%, p<0.05 at 12 months, 6.2±3.8% vs 0.3±4.6%, p<0.05 at 24 months). In the ALN group, osteocalcin and urinary deoxypyridinoline (DPD) decreased significantly at the sixth month, with no further change, by −35.6% and −63.0%, on average, respectively (p<0.05). In the control group, a significant increase in biochemical markers of bone turnover was observed in comparison to baseline values (p<0.05). PTH increased within reference levels without a difference between groups. Two nonvertebral fractures (4.2%) and nine vertebral fractures (18.8%) in the control group and three vertebral fractures (6.8%) in the ALN group occurred during the follow-up. The weekly ALN was well tolerated, and no severe side effects occurred. Conclusion This is the first randomised study including a control group to demonstrate that weekly ALN was able to significantly increase BMD in patients with OLT when compared with Ca and calcitriol alone. However, ALN did not appear to offer protection against fractures. This study was awarded the “Novartis Young Investigator Award” at the Second Joint Meeting of the European Calcified Tissue Society and the International Bone and Mineral Society, Geneva, 25–29 June 2005.