The efficacy of acute administration of pamidronate on the conservation of bone mass following severe burn injury in children: a double-blind, randomized, controlled study

Bone loss is a known complication of severe burn injury. It is, in part, due to increased endogenous glucocorticoids that contribute to the reduction in bone formation and osteoblast differentiation, hypercalciuria secondary to hypoparathyroidism, and vitamin D deficiency. In this study we attempted to prevent post-burn bone loss by acute intravenous administration of the bisphosphonate pamidronate. We enrolled 43 children, with burns of >40% total body surface area, in a randomized, double-blind, placebo-controlled study, administering the study drug within 10 days of burn injury and again 1 week later. Dual energy X-ray absorptiometry was performed prior to drug therapy, at hospital discharge and at 6 months post-burn. Urine specimens were obtained at baseline and discharge for determination of calcium and free deoxypyridinoline. Blood was obtained along with the urine specimens for measurement of intact parathyroid hormone (iPTH) and ionized calcium (Ca) levels. Following doxycycline labeling, intra-operative iliac crest bone biopsies were obtained, and bone histomorphometry was determined. At time of discharge there were no differences in total body bone mineral content (BMC), but lumbar spine BMC was significantly higher in the pamidronate group (P<0.005). By 6 months post-burn the differences in lumbar spine BMC persisted, but, now, total body BMC was significantly higher in the pamidronate group (P<0.05). Bone histomorphometry and levels of urine Ca and free deoxypyridinoline failed to show significant increases in bone formation or decreases in bone resorption. Pamidronate did not exacerbate the hypocalcemia in burn patients. In summary, acute intravenous pamidronate administration following burns may help to preserve bone mass, perhaps by inhibiting the glucocorticoid-induced apoptosis of osteoblasts and osteocytes.     

Intermittent Oral Disodium Pamidronate in Established Osteoporosis: A 2 Year Double-Masked Placebo-Controlled Study of Efficacy and Safety

The effect of oral pamidronate on bone mineral density and its adverse effect profile was investigated by a double-masked placebo-controlled study of 122 patients aged 55–75 years with established vertebral osteoporosis. Patients on active therapy received disodium pamidronate 300 mg/day (group A) for 4 weeks every 16 weeks, 150 mg/day (group B) for 4 weeks every 8 weeks or placebo (group C). All patients additionally received 500 mg of calcium and 400 IU vitamin D daily. Dual-energy X-ray absorptiometry measurements of the spine, hip, forearm and total body were performed at baseline and 6-monthly for 2 years using a Hologic QDR 1000 device at two sites. Serum osteocalcin and urinary deoxypyridinoline were measured at the above visits and at 3 months. The percentage change (SEM) in spine bone mineral density (BMD) at 2 years based on intention-to-treat analysis was 4.64 (1.01) in group A, 6.10 (0.87) in group B and 1.13 (1.32) in group C. Analysis of variance showed significant increases in group A and B compared with placebo (p<0.01). There were also significant rises in femoral neck BMD for group A (p = 0.005), trochanter BMD for groups A and B (p<0.01) and total-body BMD for groups A and B (p<0.001). There was a significant reduction in serum osteocalcin and urinary deoxypyridinoline for groups A and B (p<0.01). There was an excess of gastrointestinal side-effects in the treated groups, particularly group A. We conclude that intermittent pamidronate therapy can prevent bone loss at both the lumbar spine and femoral neck in patients with established vertebral osteoporosis, although due to gastrointestinal side-effects the 300 mg dose in particular does not appear suitable for clinical usage. Received: 12 January 1999 / Accepted: 30 August 1999     

Monitoring estrogen replacement therapy and identifying rapid bone losers with an immunoassay for deoxypyridinoline

We have assessed urinary deoxypyridinoline (Dpd) levels by immunoassay in women who participated in a double-masked, placebo-controlled trial of the bone loss prevention effects of estrogen replacement therapy (ERT). Ninety-one women who had undergone recent surgical menopause were randomdized to receive either placebo or 0.025, 0.05 or 0.1 mg/day transdermal 17β-estradiol for 2 years. Mean Dpd levels in the postmenopausal women were significantly elevated (p<0.0001) above mean Dpd levels in a reference population of healthy, premenopausal women. Subjects in the placebo group lost 6.4% of lumbar spine bone mineral density (BMD) and 4.9% of mid-radius bone mineral content (BMC) over 2 years. Dpd levels at baseline were inversely correlated with BMD and BMC changes in the placebo group. The placebo group and subjects receiving 0.025 mg/day 17β-estradiol who had Dpd levels increased above the reference interval cut-off (mean + 2 standard deviations, 7.5 nmol/mmol) lost 2 times more bone mass than did those with Dpd levels below it. Dpd levels decreased significantly (p<0.01) from baseline at 6 months following initiation of treatment with 0.05 or 0.1 mg/day 17β-estradiol, changes that correlated with increased lumbar spine BMD and with changes in mid-radius BMC. At 12 months, Dpd levels were lower than baseline and placebo in all three treatment groups. These data suggest utility of this Dpd immunoassay in assessing changes in bone resorption induced by surgical menopause and ERT.     

Bone Mineral Density During Reduction, Maintenance and Regain of Body Weight in Premenopausal, Obese Women

Weight loss may lead to bone loss but little is known about changes in bone mass during regain of reduced weight. We studied changes in bone mineral density (BMD) and bone mineral content (BMC) during voluntary weight reduction and partial regain. The study consisted of three phases: a 3 month weight reduction with very-low-energy diet (VLED), a 9 month randomized, controlled walking intervention period with two training groups (target energy expenditure 4.2 or 8.4 MJ/week) and a 24-month follow-up. The participants were premenopausal women with a mean body mass index of 34.0 (SD 3.6) kg/m². Seventy-four of 85 subjects completed the whole study. Total body, lumbar spine, proximal femur and dominant radius BMD and BMC were measured with dual-energy X-ray absorptiometry (DXA). The mean weight loss during VLED was 13.2 (3.4) kg, accompanied by unchanged total body BMC and decreased lumbar, trochanteric and radial BMD (p<0.05). During months 3–36, an average of 62% of the weight loss was regained, total body BMC decreased and trochanteric BMD increased (p<0.05). At the end of the study, total body BMC and lumbar and femoral neck BMD were lower than initially (p<0.05). Weight change throughout the study correlated significantly with the change in radial (r= 0.54), total body (r= 0.39) and trochanteric (r= 0.37) BMD. Exercise-group assignment had no effect on BMD at weight-bearing sites. In conclusion, the observed changes in BMD and BMC during weight reduction and its partial regain were clinically small and partly reversible. More studies are needed to clarify whether the observed weight changes in BMD and BMC are real or are artifacts arising from assumptions, inaccuracies and technical limitations of DXA. Received: 20 April 2000 / Accepted: 20 September 2000     

Simulated change in body fatness affects Hologic QDR 4500A whole body and central DXA bone measures.

Changes in body fatness may impact the accuracy of dual energy X-ray absorptiometry (DXA) measures of bone mineral content (BMC) and bone mineral density (BMD). The aim of this study was to determine if DXA can accurately assess BMC and BMD with changes in exogenous fat (lard) placed to simulate weight change. Whole body (WB), lumbar spine (LS), and proximal femur (PF) DXA scans (Hologic QDR 4500A) were performed on 30 elderly (52-83 yr) and 60 young (18-40 yr) individuals (i.e., 45 females and 45 males) of varying body mass index (mean+/-standard deviation: 26.1+/-4.9 kg/m2). When scans were repeated with lard packets (2.54 cm thick, 25.4x17.8 cm, 1 kg), WB BMD decreased 1.1% and 1.6% after chest and thigh packet placement, respectively (p=0.001), PF BMD increased 0.7% (p=0.02) and LS BMD decreased 1.6% (p=0.001) primarily due to a 2.2% reduction in LS BMC (p<0.001). Initial LS BMC and trunk mass were related to error in LS BMC measures due to lard-loading (r=0.64 and 0.45, respectively, p<0.001). We conclude that on average simulated weight change minimally impacts PF bone measures and moderately impacts WB and LS bone measures; however, individual variability in measurement error was noteworthy and may be impacted by body thickness.     

PIXImus Bone Densitometer and Associated Technical Measurement Issues of Skeletal Growth in the Young Rat

The PIXImus dual-energy X-ray absorptiometer (DXA) is designed to measure body composition, bone mineral content (BMC), area (BA), and density (BMD) in mice and rats. The aims of this study were to longitudinally measure BMC, BA, and BMD in growing rats and to identify potential technical problems associated with the PIXImus. Total femur and lumbar DXA measurements, body weight, and length of initially 3-week-old rats (n = 10) were taken at weeks 5, 9, and 14. BMC and BMD of femoral metaphyseal and diaphyseal regions rich in trabecular and cortical bone, respectively, were obtained. Results showed significant increases in body weight, total femur BMC and BMD, lumbar area, length, BMC, and BMD at each time point. There was a significant positive correlation between body weight and total femur BMD (r = 0.97, P < 0.001) as well as lumbar BMD (r = 0.99, P < 0.001). BMD values for the femoral metaphyseal region and the lumbar spine were also positively correlated (r = 0.96, P < 0.01). Several technical issues (e.g., positioning of animals), difficulties (e.g., in analysis of images), and limitations (e.g., inability to detect underdeveloped calcified bone in growing animals and bone edge detection) of the software pertinent to the PIXImus were evident. In conclusion, despite limitations in the software, the PIXImus is a valuable tool for studying skeletal development of growing rats.     

High bone mass in a female Hutterite population.

We examined a Hutterite population (n = 243) to determine if their agriculturally diverse, self-sufficient communal lifestyle promotes optimal bone mass attainment because of adequate calcium intake and high physical activity levels during growth and young adulthood. We measured total body (TB) and lumbar bone mineral content (BMC) and bone mineral density (BMD) in 39 school-age (younger) females and 204 working (older) females. Forty-five percent of older females and 79% of younger females currently consumed > or = 3 servings (svg) of dairy per day. Older females had lumbar (0.6 +/- 1.3) and TB (1.1 +/- 1.1) BMD Z scores greater than 0 (both, p < 0.001). The lumbar BMD Z score of younger females was not different from 0 (-0.1 +/- 1.0; p = 0.5). Both lumbar (r = 0.46; p < 0.001) and TB (r = 0.20; p = 0.02) BMD Z scores increased with increasing age. In multiple regression analyses for older females, lumbar bone area (p < 0.001), weight (p < 0.001), current hours on feet per day (p = 0.01), colony workload (p < 0.01), and estrogen status (p = 0.06) predicted lumbar BMC. TB bone area (p < 0.001), current hours on feet per day (p < 0.001), and colony workload (p < 0.01) predicted TB BMC. For younger females, lumbar bone area (p < 0.001), weight (p < 0.01), years in present colony (p = 0.02), and menses (p < 0.001) predicted lumbar BMC. TB bone area (p < 0.001), height (p < 0.01), years in present colony (p = 0.03), and menses (p < 0.01) predicted TB BMC. The effect of colony workload could not be separated from other factors different by colony. A heritability estimate of 0.66 was calculated for lumbar BMD using mother and daughter Z scores. Adequate calcium intake during growth, high physical activity early in life, and genetic factors may be contributing to above normal BMD levels in adult female Hutterites.     

Vitamin D receptor start codon polymorphism (<Emphasis Type="Italic">Fok</Emphasis>I) is related to bone mineral density in healthy adolescent boys

 Peak bone mass is considered a major determinant in the emergence of osteoporosis and is mainly genetically regulated. Several genes have been investigated, among them the vitamin D receptor (VDR) gene. A single-nucleotide polymorphism (defined by the endonuclease FokI) located in the start codon of the VDR creates the alleles F and f, resulting in different proteins. A number of previous studies have proved the F allele to be more advantageous as concerns bone mineral density (BMD). In this longitudinal study of 88 adolescent boys, we have investigated whether the different genotypes are associated with BMD, bone mineral content (BMC), or bone area. BMD, BMC, and bone area of the right femoral neck, lumbar spine, and total body were measured using dual-energy X-ray absorptiometry. Differences in phenotypes in relation to the FokI polymorphism were calculated by means of an analysis of variance (ANOVA), with Bonferroni's correction for multiple comparisons. At the first examination, the FokI genotypes were significantly related to lumbar spine BMC and total body bone area in boys aged 16.9 ± 0.3 years (mean ± SD). There was a strong tendency towards significance as regards pubertal stage, total body and femoral neck BMC, weight, lean body mass, lumbar spine bone area, and lumbar spine BMD. There were no significant differences in height, fat mass, birth height and weight, total body and femoral neck BMD, and femoral neck bone area. Regression analysis proved the FokI genotypes to be independently related to lumbar spine BMD (FF > ff; P < 0.01), and possibly total body BMD (P = 0.06), but not femoral neck BMD. At the second examination, approximately 2 years later, our ANOVA results showed significance as regards femoral neck BMC and weight. Using multiple regression, the FokI genotypes were independently related to lumbar spine BMD (FF > ff; P = 0.03), and total body BMD (P < 0.05), but not femoral neck BMD. This study proves the FokI polymorphism to be an independent predictor of lumbar spine BMD are probably total body BMD, but not femoral neck BMD. Received: December 25, 2001 / Accepted: October 7, 2002 Offprint requests to: M. Lorentzon     

Nandrolone decanoate and intranasal calcitonin as therapy in established osteoporosis

This study used a randomized, 2 × 2 factorial design to evaluate over 2 years the effect of intranasal salmon calcitonin and intramuscular nandrolone decanoate on bone mass in elderly women with established osteoporosis. The study was double masked in relation to calcitonin and open in relation to nandrolone decanoate. One hundred and twenty-three women aged 60–88 years who had sustained a previous osteoporotic fracture, or had osteopenia, were recruited through an outpatient clinic. Women were assigned to one of four groups: (1) daily placebo nasal spray, (2) 400 IU intranasal calcitonin daily, (3) 20 intramuscular injections of 50 mg nandrolone decanoate (given as two courses of 10 injections) plus placebo nasal spray, or (4) 20 injections of 50 mg nandrolone decanoate plus 400 IU intranasal calcitonin daily. All subjects received 1000 mg calcium supplementation daily. Outcomes measured included changes in bone mineral density (BMD) at the lumbar spine, as measured by dual-energy quantitative computed tomography (DEQCT), in BMD of the proximal femur, and BMD and bone mineral content (BMC) of the lumbar spine and forearm, as measured by dual-energy X-ray absorptiometry (DXA). Significant positive changes from baseline in DXA BMC at the lumbar spine were observed over 2 years in the calcitonin group (5.0±1.9%, mean ± SE) and in the nandrolone deconate group (4.7±1.9%) but not in the placebo group (1.1±2.2%) or the combined therapy group (0.7±1.8%). Modelling based on the 2×2 factorial design revealed that nandrolone decanoate was associated with a 3.8±1.8% (p<0.05) gain in DXA BMD at the proximal femur. Modelling also revealed that calcitonin treatment was associated with a loss of 11.5±4.7% in DEQCT BMD at the lumbar spine and a loss of 3.7±1.8% in DXA BMD at the proximal femur (p<0.05). There was in vivo antagonism between the two medications of 7.9±3.9% for DXA BMC at the lumbar spine. Both agents caused positive changes from baseline in lumbar spine BMC. Nandrolone decanoate had beneficial effects on BMD at the proximal femur. This dose of intranasal calcitonin was associated with deleterious effects on trabecular BMD at the lumbar spine and total BMD at the proximal femur. There may be significant clinical antagonism between these two medications.     

Catch up in bone acquisition in young adult men with late normal puberty

The aim of this study was to investigate the development of bone mineral density (BMD) and bone mineral content (BMC) in relation to peak height velocity (PHV), and to investigate whether late normal puberty was associated with remaining low BMD and BMC in early adulthood in men. In total, 501 men (mean ± SD, 18.9 ± 0.5 years of age at baseline) were included in this 5‐year longitudinal study. Areal BMD (aBMD) and BMC, volumetric BMD (vBMD) and cortical bone size were measured using dual‐energy X‐ray absorptiometry (DXA) and pQCT. Detailed growth and weight charts were used to calculate age at PHV, an objective assessment of pubertal timing. Age at PHV was a strong positive predictor of the increase in aBMD and BMC of the total body (R² aBMD 11.7%; BMC 4.3%), radius (R² aBMD 23.5%; BMC 22.3%), and lumbar spine (R² aBMD 11.9%; BMC 10.5%) between 19 and 24 years (p < 0.001). Subjects were divided into three groups according to age at PHV (early, middle, and late). Men with late puberty gained markedly more in aBMD and BMC at the total body, radius, and lumbar spine, and lost less at the femoral neck (p < 0.001) than men with early puberty. At age 24 years, no significant differences in aBMD or BMC of the lumbar spine, femoral neck, or total body were observed, whereas a deficit of 4.2% in radius aBMD, but not in BMC, was seen for men with late versus early puberty (p < 0.001). pQCT measurements of the radius at follow‐up demonstrated no significant differences in bone size, whereas cortical and trabecular vBMD were 0.7% (p < 0.001) and 4.8% (p < 0.05) lower in men with late versus early puberty. In conclusion, our results demonstrate that late puberty in males was associated with a substantial catch up in aBMD and BMC in young adulthood, leaving no deficits of the lumbar spine, femoral neck, or total body at age 24 years. © 2012 American Society for Bone and Mineral Research.     

Bone mass and density in preadolescent boys with and without Down syndrome

Summary

Preadolescent boys with Down syndrome at 7–10 years of age have lower bone mass and density in the pelvis than age-matched children without Down syndrome. However, bone mass and density of total body less head and lumbar spine are not different between these two groups.

Introduction

This study aimed to assess bone mineral content (BMC) and density (BMD) in preadolescent boys with and without Down syndrome (DS) at 7–10 years of age.

Methods

Eleven preadolescent boys with DS and eleven age-matched children without DS participated in this study. Dual-energy X-ray absorptiometry was used to measure BMC and BMD in whole body and lumbar spine. Both BMC and BMD of total body less head (TBLH) and lumbar spine (vertebrae L2–L4) were compared between the two groups, with and without adjusting for physical characteristics such as bone area, body height, and total lean mass. Two bone mineral apparent density (BMAD) variables were calculated to estimate volumetric BMD in the lumbar spine.

Results

Both BMC and BMD in the pelvis were lower in the DS group, after adjusting for physical characteristics. However, with and without adjusting for physical characteristics, the two groups were not different in BMC and BMD of the arms, legs, and TBLH from the whole body scan and in BMC, BMD, and BMAD of the lumbar spine from the lumbar spine scan.

Conclusions

These findings indicate that the pelvis may be the first site to show the significant difference in BMC and BMD between preadolescent boys with and without DS. It also suggests that significantly lower BMC and BMD in whole body and lumbar spine, which is usually observed in young adults with DS, may not occur before adolescence.     

Collagen Ialpha1 polymorphism is associated with bone characteristics in Caucasian children and young adults

A large proportion of the variation in bone mass can be explained by genetic factors. We analyzed the G to T substitution in the Sp1 binding site in the first intron of the collagen type Ialpha1 (COLIA1) gene in relation to bone mass. The genotypes GG, GT, and TT were determined in 148 Caucasian children and young adults. We performed dual energy X-ray absorptiometry twice (mean follow-up time 4.4 years), and speed of sound (SOS) was assessed by tibial ultrasonometry at follow-up. Genotype distribution was 104 (70%) GG, 40 (27%) GT and 4 (3%) TT. Carriers of the T-allele had a 0.5 SDS (standard deviation score) decreased bone mineral content (BMC) of total body (P = 0.001), and a 0.4 SDS decreased bone mineral density (BMD) for both lumbar spine (P = 0.04) and total body (P = 0.05). The genotype effect on BMD and BMC decreased after adjustment for height or body mass index. When we calculated apparent BMD, these differences diminished to 0.1 SDS and were no longer significant. T-allele carriers had shorter stature (0.4 SDS; P = 0.04) and smaller bones (0.5 SDS lower width of the lumbar vertebral body; P = 0.01). The T-allele was also associated with lower SOS (P = 0.03), independent of BMD and BMC, and lower lean body mass. Similar associations were found at follow-up. The change in BMD and BMC SDS between the first and second measurement did not differ between the GG and GT&TT group. In conclusion, the COLIA1 polymorphism in children and young adults is associated with several bone characteristics. However, at least a part of the COLIA1 effect on bone mass may be related to differences in frame size.     

Intravenous pamidronate treatment in children with moderate to severe osteogenesis imperfecta: assessment of indices of dual-energy X-ray absorptiometry and bone metabolic markers during the first year of therapy

Bisphosphonates are now widely used to treat children with osteogenesis imperfecta (OI). However, there are few published data following the initial evolution of changes in bone mass with such treatment. The purpose of the present study was to assess indices of skeletal size and total and regional bone mass in children with OI during the first year of their pamidronate therapy. Twenty-six children [11 males, age median 10.6 (range 3.2-15.5) years] with type III (n=9) or type IV (n=17) OI received intravenous pamidronate 1.0 mg/kg/day on 3 consecutive days, 3-monthly over a 1-year period. Bone mass assessed by dual energy X-ray absorptiometry, serum alkaline phosphatase (ALP) and urine type I collagen N-terminal telopepetide (NTX) were measured at each cycle. Lumbar (L2 to L4) vertebral height increased by median (interquartile range) 4.5% (7.3), area by 11.3% (19.3), bone mineral content (BMC) by 73.7% (50.4), and bone mineral density (BMD) by 48.7% (34.7), P<0.0001 during the first year of therapy. Total body bone area increased by 26.7% (26.3), total body BMC by 41.4% (44.5), and total body BMD by 8.8% (8.3), P<0.0001. Head bone area remained constant whilst head BMC and BMD increased. Pre-infusion U-NTX and S-ALP levels decreased progressively during the follow-up indicating reducing bone turnover rate during pamidronate therapy. Increased bone area and mineral mass were observed during the first year of intravenous pamidronate therapy in children with OI. Increased head bone mass implies a direct effect of pamidronate on skeletal mass accretion, rather than an indirect effect mediated through increased physical activity.     

Pamidronate reduces PTH-mediated bone loss in a gene transfer model of hyperparathyroidism in rats.

We evaluated spinal and femoral bone mass and density utilizing dual-energy x-ray absorptiometry (DEXA) in rats in which severe hyperparathyroidism was produced by the expression of the gene for human PTH-(1-84) (hPTH). This gene was incorporated into a retroviral vector that was transfected into fibroblasts which were subsequently injected into their peritoneal cavities. Further, we examined the effect of the administration of pamidronate on bone mass and density in the presence of extremely high concentrations of hPTH. Three groups of rats were studied. Groups 1 and 2 receive the hPTH-secreting fibroblasts; group 2 subsequently received pamidronate (2.5 mg/kg IV) 18 and 27 days after receiving the fibroblasts. These animals developed levels of hPTH greater than 1.0 microgram/liter and became hypercalcemia within 20 days. These animals became lethargic and were significantly lower in weight than age-matched controls (group 3, p less than 0.05). After accounting for the animal weight there was a further significant decrease in bone mineral content and density (BMC and BMD) on day 29 attributable to hPTH-mediated bone loss. Treatment with pamidronate resulted in a higher BMC of the lumbar spine than in the untreated animals, with elevated concentrations of hPTH. The BMD was significantly higher at both the lumbar spine and femur in the pamidronate-treated animals (p less than 0.05). The CV of paired measurements of BMD was 2.7% at the spine and 1.5% of a femur, respectively. The BMC of the lumbar spine and femur was closely correlated with the ashed weight of the same bones (r = 0.92 and 0.85, respectively).     

Correlation between hand and total body bone density in normal Chinese children

Hand bone mineral density (BMD) in adults was found to be significantly correlated with various skeletal sites, including the total body. However, the relationships between hand and total body bone measurements have yet to be explored for children. We conducted a cross-sectional study of 892 normal Chinese children (511 males, 381 females) aged 5-14 years by measuring the BMD and bone mineral content (BMC) at the total hand, upper limb, subtotal body, and total body using dual-energy X-ray absorptiometry (DXA). We found that hand BMD and BMC increased with age for both genders. Female children had significantly higher hand BMD and BMC than males. Age explained more variance in hand BMD for females (R2=0.727) than for males (R2=0.596). For both genders, hand BMD and BMC correlated highly with age, weight, height, total body lean mass, and BMD and BMC at the upper limb, subtotal body, and total body (r=0.730-0.965, p<0.001) and moderately with body mass index and total body fat mass (r=0.525-0.701, p<0.001). Therefore, the hand DXA scan can potentially be a new tool for the clinical assessment of bone health in children.     

Role of oral pamidronate in preventing bone loss in postmenopausal women

We have performed a 2-year prospective double-masked study to determine whether the bisphosphonate pamidronate can prevent bone loss in postmenopausal women and its optimal dosage regimen. One hundred and twenty-one such women (mean ± SD age 57.6±3.4 years; mean ± SD time since menopause 7.5±3.5 years) were randomized to receive either oral pamidronate (300 mg/day) for 4 weeks every 4 months (group A), oral pamidronate (150 mg/day) for 4 weeks every 2 months (group B) or identical placebo capsules (group C). Bone mineral density (BMD) measurements at the lumbar spine and proximal femur were performed at baseline and at 6-month intervals for 2 years using dual-energy X-ray absorptiometry. BMD at the lumbar spine (L2–4) increased significantly in groups A and B after 2 years of treatment (mean ± SD 2.8±2.1% and 3.0±2.9% respectively, bothp<0.001) but decreased in the placebo group (–1.6±3.1%,p<0.01). Identical results were seen for BMD at the femoral neck, which increased significantly in groups A and B after 2 years of treatment (1.2±2.3% and 1.3±2.9% respectively, bothp<0.05) but decreased in the placebo group (–1.9±3.9%,p<0.05). There were significant differences over 2 years between the groups at all anatomical sites (lumbar spine, femoral neck and trochanteric region, allp<0.001; Ward's triangle,p<0.01). However, there were no significant differences between groups A and B, suggesting that the two treatment regimens were equally effective in conserving BMD. There were, however, marked differences in tolerability between the two treatment regimens: 13 women (34%) in group A withdrew from the study because of side-effects, but only 5 women (12%) in group B, which was comparable with placebo. These data demonstrate that intermittent oral pamidronate will prevent bone loss from the lumbar spine and proximal femur of postmenopausal women, and that the more frequent but lower dose regimen is well tolerated.     

Initial years of recreational artistic gymnastics training improves lumbar spine bone mineral accrual in 4- to 8-year-old females.

Gymnasts' bone mineral characteristics are generally not known before starting their sport. Prepubertal females who enrolled in beginning artistic gymnastics (n = 65) had lower bone mineral than controls (n = 78). However, 2 years of gymnastics participation versus no participation led to a significantly greater accrual of forearm bone area and lumbar spine areal BMD. INTRODUCTION: The skeletal response to exercise in children compared with adults is heightened because of the high bone turnover rate and the ability of bone to change its size and shape. Whereas child gymnasts generally have greater rates of bone mineral accrual compared with nongymnasts, it is unknown if some of these skeletal advantages are present before the onset of training or are caused entirely by training. MATERIALS AND METHODS: Changes in bone area (BA; cm2), BMC (g), and areal BMD (aBMD; g/cm2) over 24 months were examined in prepubertal females, 4-8 years of age, who selected to perform recreational gymnastics (GYM; n = 65), nongymnastic activities, or no organized activity (CON; n = 78). Participants had essentially no lifetime history of organized athletic participation (< 12 weeks). Pubertal maturation was assessed annually by a physician. Total body, lumbar spine, total proximal femur, and forearm BA, BMC, and aBMD were measured every 6 months using DXA (Hologic QDR-1000W). Independent samples t-tests determined baseline group differences. Nonlinear mixed effects models were used to model 24-month changes in bone data. In subset analyses, high-level gymnasts advancing to competition (HLG; n = 9) were compared with low-level nonadvancing gymnasts (LLG; n = 56). RESULTS: At baseline, GYM were shorter, lighter, and had lower BA, BMC, and aBMD compared with CON (p < 0.05), whereas HLG did not differ significantly in these measurements compared with LLG (p > 0.05). Controlling for differences in race, baseline measures of body mass, height, and calcium intake, and change in breast development beyond stage II at 24 months, GYM had greater long-term (asymptotic) mean responses for total body aBMD and forearm BMC (p < 0.04) and greater rates of increase in the mean responses of lumbar spine aBMD and forearm BA compared with CON over 24 months. Over time, forearm BA increased to a greater extent in HLG compared with LLG (p < 0.01). CONCLUSIONS: Females participating in recreational gymnastics initiated during childhood have enhanced bone mineral gains at the total body, lumbar spine, and forearm over 24 months. Higher-level training promotes additional gains in forearm BA.     

The impact of degenerative conditions in the spine on bone mineral density and fracture risk prediction

We examined the impact of degenerative conditions in the spine (osteophytosis and endplate sclerosis) and aortic calcification in the lumbar region on bone mineral content/density (BMC/BMD) measured in the spine and forearm by absorptiometry and on fracture risk prediction. The radiographs of 387 healthy postmenopausal women, aged 68–72 years, were assessed in masked fashion for the presence of osteophytosis, endplate sclerosis and aortic calcification in the region from L2 to L4. Vertebral deformities/fractures were assessed by different definitions. Osteophytes larger than 3 mm and in numbers of 3 or more resulted in a significantly (12%) higher spinal bone mass (p<0.001). Endplate sclerosis had a similar effect (p<0.001). In subjects with both degenerative conditions the BMC/BMD in the spine and forearm were significantly higher than in unaffected women (19% in the spine, 10% in the forearm;p<0.001). The spinal BMD values were significantly lower in fractured women if both degenerative conditions were absent (p<0.001), whereas fractured and unfractured women had similar values if degenerative conditions were present. Degenerative conditions did not alter the ability of forearm BMC to discriminate vertebral or peripheral fractures. Receiver operating characteristic (ROC) curves (true positive fraction versus false positive fraction) were generated for BMD of the lumbar spine and BMC of the forearm with regard to the discrimination between women with vertebral and peripheral fractures and healthy premenopausal women. The ROC curves for women without degenerative conditins were consistently above the curves for women affected by osteophytosis and endplate sclerosis in the lumbar spine (p<0.001). In conclusion, osteophytes and endplate sclerosis have a considerable influence on spinal bone mass measurements in elderly postmenopausal women and affect the diagnostic ability of spinal scans to discriminate osteoporotic women. Our data suggest that in elderly women, unless the spine is radiologically clear of degenerative conditions, a peripheral measurement procedure should be considered an alternative for assessment of bone mineral content/ensity.     

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.     

体重、身高对成都地区青壮年腰椎、髋部骨量的影响

目的　研究体重、身高对青壮年腰椎、髋部骨量的影响。方法　随机抽取成都地区年龄在 2 0～ 39岁 ,排除心肝肺肾、内分泌等慢性病、骨代谢疾病及脊椎畸形者 2 37名 (其中男性 10 8名 ,女性 12 9名 ) ,采用美国Lunar公司生产DPX L型双能X线骨密度仪测定受试者腰椎和髋部的骨矿含量 (BMC)、面积 (AREA)、骨密度 (BMD)。全部资料输入微机 ,用SPSS软件进行统计学处理。结果　体重、身高、体重指数 (BMI)与腰椎、髋部的BMC、Area、BMD呈正相关 ,其中体重与腰椎、髋部的BMC、Area中等程度相关 (r=0 39～ 0 5 5 ,P <0 0 1) ,身高与腰椎 (L2 - 4)AREA相关性最好 (r=0 75 8,P <0 0 1) ,体重、身高与BMD相关性差 (r=0 15 2～ 0 2 2 5 ,P <0 0 5 )。男性腰椎及髋部的BMC、AREA均明显高于同年龄组女性 (P <0 0 1) ,男、女L2 - 4BMD无显著性差异 (P >0 0 5 ) ,男性略低于女性。L2 - 4BMC与体重比值及L2 - 4AREA与体重比值 ,男、女无显著性差异 (P >0 0 5 )。L2 - 4Area与身高比值男性明显高于女性 (P <0 0 1)。结论　体重对青壮年BMC的影响大于身高 ,身高对L2 - 4AREA影响最大 ,男、女体重、身高的差异决定了峰值骨量的差异。BMC、Area、BMD 3项指标中 ,BMC更能反映体重、身高的差异 ,用BMC诊断骨质疏松