Body Areal Bone Mineral Density Research Articles

Differences in bone mineral density and associated factors in dancers and other female athletes.

Dancers are susceptible to relative energy deficiency in sport (RED-S), specifically low bone mineral density (BMD). Little is known about how dancers' BMD compares to other athletic populations. The objective of this study was to examine the association between participant characteristics and total body areal BMD (aBMD) among female pre-professional dancers compared to other female athletes. Two hundred sixty-nine females (132 pre-professional dancers (17.6 (3.2) years) and 137 sport participants (22.8 (2.6) years) were included in this study. aBMD (g/cm2) was estimated using dual X-ray absorptiometry. Multivariable linear regression was used to examine the association between height-adjusted z-scores of total body aBMD (aBMD-Z) and age (years), body mass index (BMI) (z-score), supplement intake, history of stress fracture, irregular menses, MRI/bone scan, 1-year injury history, oral contraceptives, and activity (dance/sport). Total body aBMD and aBMD-Z were lower in dancers than athletes (dancers: aBMD=1.03g/cm2 (95% CI: 1.01, 1.05); aBMD-Z = -0.28 (-0.43, -0.12) (p<0.001); athletes: aBMD=1.14g/cm2 (95% CI: 1.12, 1.16); aBMD-Z=0.41 (0.25, 0.57) (p<0.001)). aBMD-Z increased with age (β = 0.054, 95% CI: 0.017, 0.092; p=0.004) and BMI (β = 0.221, 95% CI: 0.006, 0.415; p=0.043). Activity type modified the relationship between BMI and aBMD-Z (β = 0.323, 95% CI: 0.025, 0.621; p<0.033) with a stronger positive association in dancers, compared to other female athletes. Dancers had lower total body aBMD and aBMD-Z than other female athletes. aBMD-Z increases with age in female pre-professional dancers and other female athletes. A stronger association exists between aBMD-Z and BMI in dancers than athletes. Future studies should consider changes in aBMD-Z during adolescence and associations with increased risk of bone injury.

Loss of Nmp4 enhances bone gain from sclerostin antibody administration.

Severe osteoporosis is often treated with one of three Food and Drug Administration (FDA)-approved osteoanabolics. These drugs act by (1) parathyroid hormone (PTH) receptor stimulation using analogues to PTH (teriparatide) or PTH-related peptide (abaloparatide) or by (2) monoclonal antibody neutralization of sclerostin, an innate Wnt inhibitor (Scl-mAb, romosozumab-aqqg). The efficacies of both strategies wane over time. The transcription factor Nmp4 (Nuclear Matrix Protein 4) is expressed in all tissues yet mice lacking this gene are healthy and exhibit enhanced PTH-induced bone formation. Conditional deletion of Nmp4 in mesenchymal stem progenitor cells (MSPCs) phenocopies the elevated response to PTH in global Nmp4-/- mice. However, targeted deletion in later osteoblast stages does not replicate this response. In this study we queried whether loss of Nmp4 improves Scl-mAb potency. Experimental cohorts included global Nmp4-/- and Nmp4+/+ littermates and three conditional knockout models. Nmp4-floxed (Nmp4fl/fl) mice were crossed with mice harboring one of three Cre-drivers (i) Prx1Cre+ targeting MSPCs, (ii) BglapCre+ (mature osteocalcin-expressing osteoblasts), and (iii) Dmp1Cre+ (osteocytes). Female mice were treated with Scl-mAb or 0.9% saline vehicle for 4 or 7weeks from 10weeks of age. Skeletal response was assessed using micro-computed tomography, dual-energy X-ray absorptiometry, bone histomorphometry, and serum analysis. Global Nmp4-/- mice exhibited enhanced Scl-mAb-induced increases in trabecular bone in the femur and spine and a heightened increase in whole body areal bone mineral density compared to global Nmp4+/+ controls. This improved Scl-mAb potency was primarily driven by enhanced increases in bone formation. Nmp4fl/fl;PrxCre+ mice showed an exaggerated Scl-mAb-induced increase in femoral bone but not in the spine since Prrx1 is not expressed in vertebra. The Nmp4fl/fl;BglapCre+ and Nmp4fl/fl;Dmp1Cre+ mice did not exhibit an improved Scl-mAb response. We conclude that Nmp4 expression in MSPCs interferes with the bone anabolic response to anti-sclerostin therapy.

Cannabidiol-Treated Ovariectomized Mice Show Improved Glucose, Energy, and Bone Metabolism With a Bloom in Lactobacillus.

Loss of ovarian 17β-estradiol (E2) in postmenopause is associated with gut dysbiosis, inflammation, and increased risk of cardiometabolic disease and osteoporosis. The risk-benefit profile of hormone replacement therapy is not favorable in postmenopausal women therefore better treatment options are needed. Cannabidiol (CBD), a non-psychotropic phytocannabinoid extracted from hemp, has shown pharmacological activities suggesting it has therapeutic value for postmenopause, which can be modeled in ovariectomized (OVX) mice. We evaluated the efficacy of cannabidiol (25 mg/kg) administered perorally to OVX and sham surgery mice for 18 weeks. Compared to VEH-treated OVX mice, CBD-treated OVX mice had improved oral glucose tolerance, increased energy expenditure, improved whole body areal bone mineral density (aBMD) and bone mineral content as well as increased femoral bone volume fraction, trabecular thickness, and volumetric bone mineral density. Compared to VEH-treated OVX mice, CBD-treated OVX mice had increased relative abundance of fecal Lactobacillus species and several gene expression changes in the intestine and femur consistent with reduced inflammation and less bone resorption. These data provide preclinical evidence supporting further investigation of CBD as a therapeutic for postmenopause-related disorders.

Effects of a Home-Based Exercise Intervention (E-Fit) on Bone Density, Muscle Function, and Quality of Life in Girls with Adolescent Idiopathic Scoliosis (AIS): A Pilot Randomized Controlled Trial.

Background: Adolescent idiopathic scoliosis (AIS) patients have lower physical activity levels than normal adolescents, and there is an association with poorer bone and muscle health. This study evaluated the effects of a home-based exercise intervention (E-Fit) on bone mineral density (BMD), muscle function, and quality of life (QoL) in AIS-affected girls. Methods: A total of 40 AIS females aged 11 to 14 years were randomly assigned to the E-Fit or control group. The E-Fit group performed modified 7-min high-intensity interval training (HIIT) 5 days per week for 6 months. Outcome measures including BMD using dual-energy X-ray absorptiometry (DXA), muscle strength and endurance tests, physical activity levels, and QoL using self-reported questionnaires were assessed at baseline and at 6-month and 12-month follow-up. Results: In total, 14 patients in the E-Fit and 16 in the control group completed the study. The E-Fit group showed a marginally significant interaction effect in the whole body areal BMD at the 6- (p = 0.096) and 12-month follow-ups (p = 0.085). The left arm lean mass in the E-Fit group showed a statistically significant interaction effect between the 6- and 12-month follow-ups (p = 0.046). The E-Fit group showed improvements in physical activity participation, as measured by the Modified Baecke Questionnaire (MBQ), with a significant interaction effect in work index (p = 0.043), sport index (p = 0.050), and total score (p = 0.016) from baseline to the 12-month follow-up. Improvement on self-image were noted in E-Fit group across time. Conclusions: The present results provided some evidence to support the positive benefits of E-Fit for bone health and muscle function in AIS girls.

Membrane estrogen receptor α is essential for estrogen signaling in the male skeleton.

The importance of estrogen receptor α (ERα) for the regulation of bone mass in males is well established. ERα mediates estrogenic effects both via nuclear and membrane-initiated ERα (mERα) signaling. The role of mERα signaling for the effects of estrogen on bone in male mice is unknown. To investigate the role of mERα signaling, we have used mice (Nuclear-Only-ER; NOER) with a point mutation (C451A), which results in inhibited trafficking of ERα to the plasma membrane. Gonadal-intact male NOER mice had a significantly decreased total body areal bone mineral density (aBMD) compared to WT littermates at 3, 6 and 9 months of age as measured by dual-energy X-ray absorptiometry (DEXA). High-resolution microcomputed tomography (µCT) analysis of tibia in 3-month-old males demonstrated a decrease in cortical and trabecular thickness in NOER mice compared to WT littermates. As expected, estradiol (E2) treatment of orchidectomized (ORX) WT mice increased total body aBMD, trabecular BV/TV and cortical thickness in tibia compared to placebo treatment. E2 treatment increased these skeletal parameters also in ORX NOER mice. However, the estrogenic responses were significantly decreased in ORX NOER mice compared with ORX WT mice. In conclusion, mERα is essential for normal estrogen signaling in both trabecular and cortical bone in male mice. Increased knowledge of estrogen signaling mechanisms in the regulation of the male skeleton may aid in the development of new treatment options for male osteoporosis.

Adiposity, Insulin Resistance, and Bone Mass in Children and Adolescents.

Insulin resistance is an adverse health outcome that accompanies obesity. Fat mass is negatively associated with the bone mass after adjustment for confounders. Insulin resistance might be an intermediary in this relationship. To determine whether insulin resistance is an intermediary in the relationship between adiposity and bone mass in adolescents. Cross-sectional secondary analysis of baseline data from a previous randomized trial. University research facility. A total of 240 adolescents (68% female), aged 7 to 15 years. Using dual energy x-ray absorptiometry, bone mineral content (BMC), areal bone mineral density, lean mass, and fat mass were measured. Skeletal sites of interest included the total body and lumbar spine (LS). Waist circumference was measured using an anthropometric tape measure. Insulin and glucose were measured in fasting sera, and the homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Path analysis was performed to determine whether the relationship between adiposity and bone was mediated through insulin resistance. Fat mass (r = 0.467; P < 0.001) and waist circumference (r = 0.487; P < 0.001) correlated positively with HOMA-IR. Controlling for race, sex, maturation, lean mass, and height, fat mass, waist circumference, and HOMA-IR were negatively associated with LS BMC and total body areal bone mineral density (P < 0.05 for all). Additionally, path models for fat mass (95% CI, -5.893 to -0.956) and waist circumference (95% CI, -15.473 to -2.124) showed a negative relationship with LS BMC via HOMA-IR. These results support an intermediary role of insulin resistance in the relationship between adiposity and LS bone mass.

Fat mass is positively associated with bone mass acquisition in children with small or normal lean mass: A three-year follow-up study.

The independent impact of fat mass (FM) on bone health is difficult to assess, as FM is correlated with lean soft tissue mass (LSTM). In a previous cross-sectional study, FM was suggested to help promote high bone mass acquisition in adolescents with small LSTM. The present prospective cohort study investigated the effects of FM on bone in pubertal children after stratification by height-normalized index of LSTM (LSTMI). The source population was all 5th grade children enrolled in either one of the two public elementary schools in Hamamatsu, Japan. Of these, 545 children who participated in both baseline (at age 11) and follow-up (at age 14) surveys were included in the present analysis. Body composition and whole body areal bone mineral density (aBMD) were measured using dual-energy X-ray absorptiometry. From baseline to follow-up, significant (P<0.05) differences were observed in changes in aBMD among tertiles of change in FM in both sexes after adjusting for confounding factors including LSTMI. After stratification by tertiles of sex-specific LSTMI, adjusted means of changes in aBMD according to tertiles of change in FM within the lowest and second lowest tertiles of LSTMI in both sexes showed a significant increase from the lower tertiles to the highest tertile of change in FM. In the highest tertile of LSTMI, changes in FM showed no significant association with changes in aBMD. These findings suggest that adipose tissue might help promote high bone mass acquisition in pubertal children with small or normal LSTMI.

Effects of low-dose ibuprofen supplementation and resistance training on bone and muscle in postmenopausal women: A randomized controlled trial

PurposeTo compare the effects of nine months of exercise training and ibuprofen supplementation (given immeditately after exercise sessions) on bone and muscle in postmenopausal women. MethodsIn a double-blind randomized trial, participants (females: n=90, mean age 64.8, SD 4.3years) were assigned (computer generated, double blind) to receive supervised resistance training or stretching 3days/week, and ibuprofen (400mg, post-exercise) or placebo (i.e. 4 groups) for 9months. In this proof-of-concept study the sample size was halved from required 200 identified via 90% power calculation. Baseline and post-intervention testing included: Dual energy x-ray absorptiometry (DXA) for lumbar spine, femoral neck, and total body areal bone mineral density (aBMD); geometry of proximal femur; total body lean tissue and fat mass; predicted 1-repetition maximum muscle strength testing (1RM; biceps curl, hack squat). ResultsExercise training or ibuprofen supplementation had no effects on aBMD of the lumbar spine, femoral neck, and total body. There was a significant exercise×supplement×time interaction for aBMD of Ward's region of the femoral neck (p=0.015) with post hoc comparison showing a 6% decrease for stretching with placebo vs. a 3% increase for stretching with ibuprofen (p=0.017). Resistance training increased biceps curl and hack squat strength vs. stretching (22% vs. 4% and 114% vs. 12%, respectively) (p<0.01) and decreased percent body fat compared to stretching (2% vs. 0%) (p<0.05). ConclusionsIbuprofen supplementation provided some benefits to bone when taken independent of exercise training in postmenopausal women. This study provides evidence towards a novel, easily accessible stimulus for enhancing bone health [i.e. ibuprofen].

The role of activation functions 1 and 2 of estrogen receptor-α for the effects of estradiol and selective estrogen receptor modulators in male mice

Estradiol (E2) is important for male skeletal health and the effect of E2 is mediated via estrogen receptor (ER)-α. This was demonstrated by the findings that men with an inactivating mutation in aromatase or a nonfunctional ERα had osteopenia and continued longitudinal growth after sexual maturation. The aim of the present study was to evaluate the role of different domains of ERα for the effects of E2 and selective estrogen receptor modulators (SERMs) on bone mass in males. Three mouse models lacking either ERαAF-1 (ERαAF-1(0)), ERαAF-2 (ERαAF-2(0)), or the total ERα (ERα(-/-)) were orchidectomized (orx) and treated with E2 or placebo. E2 treatment increased the trabecular and cortical bone mass and bone strength, whereas it reduced the thymus weight and bone marrow cellularity in orx wild type (WT) mice. These parameters did not respond to E2 treatment in orx ERα(-/-) or ERαAF-2(0). However, the effects of E2 in orx ERαAF-1(0) [corrected] were tissue-dependent, with a clear response in cortical bone parameters and bone marrow cellularity, but no response in trabecular bone. To determine the role of ERαAF-1 for the effects of SERMs, we treated orx WT and ERαAF-1(0) mice with raloxifene (Ral), lasofoxifene (Las), bazedoxifene (Bza), or vehicle. These SERMs increased total body areal bone mineral density (BMD) and trabecular volumetric BMD to a similar extent in orx WT mice. Furthermore, only Las increased cortical thickness significantly and only Bza increased bone strength significantly. However, all SERMs showed a tendency toward increased cortical bone parameters. Importantly, all SERM effects were absent in the orx ERαAF-1(0) mice. In conclusion, ERαAF-2 is required for the estrogenic effects on all evaluated parameters, whereas the role of ERαAF-1 is tissue-specific. All evaluated effects of Ral, Las and Bza are dependent on a functional ERαAF-1. Our findings might contribute to the development of bone-specific SERMs in males.

Does maternal long chain polyunsaturated fatty acid status in pregnancy influence the bone health of children? The Southampton Women's Survey.

In this large, population-based, prospective, mother-offspring cohort study, maternal long chain polyunsaturated fatty acid (LCPUFA) status during pregnancy was found to be positively associated with bone mass in the offspring at age 4years. The findings suggest that variation in intrauterine exposure to n-3 and n-6 LCPUFAs may have potential consequences for skeletal development. Maternal diet in pregnancy has been linked to childhood bone mass, but the mechanisms and nutrients involved are uncertain. Long-chain polyunsaturated fatty acids (LCPUFAs) have been shown to affect bone metabolism, but the relationship between maternal fatty acid status and bone mass in the offspring remains unknown. We evaluated the association between maternal LCPUFA status in late pregnancy (34weeks gestation) and bone density in their children at age 4years within 727 mother-child pairs taking part in the Southampton Women's Survey. Concentrations of the n-3 LCPUFA component of maternal plasma phosphatidylcholine were positively associated with a number of bone mineral measures at the age of 4years; these associations persisted after adjustment for maternal body build, walking speed and infant feeding. Relationships were most evident for eicosapentaenoic acid (r = 0.09, p = 0.02 for whole body areal bone mineral density [aBMD] and r = 0.1, p = 0.008 for lumbar spine aBMD) and for docosapentaenoic acid (r = 0.09, p = 0.02 for whole body aBMD and r = 0.12, p = 0.002 for lumbar spine aBMD). These findings suggest that variation in early exposure to n-3 and n-6 LCPUFA may have potential consequences for bone development and that the effects appear to persist into early childhood.

Determinants of bone mineral density, bone mineral content, and body composition in a cohort of healthy children: influence of sex, age, puberty, and physical activity

Interventions directed to the recognition of abnormal bone mineral density, bone mineral content, and body composition in the pediatric age require the definition of factors influencing bone mass acquisition during growth. We have evaluated in a cross-sectional manner by dual-energy X-ray absorptiometry the impact of sex, age, puberty, and physical activity on total body areal bone mineral density, regional (lumbar and femoral) bone mineral densities, bone mineral content, and body composition (fat mass and lean mass) in a cohort of 359 healthy Italian children aged 3-14 years and investigated their specific contribution to bone mass accrual. Statistical multiple regression analysis was performed dividing the population in pre- and post-pubertal groups. Bone mineral density at the lumbar spine has resulted equally distributed in both sexes before puberty while has resulted higher at the femoral necks in males at whatever age. A significant effect on bone mass acquisition was exerted by male sex and lean mass. In the areas where the cortical bone is prevalent, males of the pre-pubertal group have presented the highest values; in the areas where the cancellous bone is prevalent, both sexes were equivalent until the age of 9 years, but after this age, females have presented higher increases, probably related to the inferior dimensional development of lumbar vertebrae. Conclusively, male sex and lean mass seem to represent independent predictors of bone mass accrual in the cortical bone of the examined children, while female sex and pubertal maturation are independent predictors of bone mass accrual in the trabecular bone.

Vertebral fractures despite normal spine bone mineral density in a boy with nephrotic syndrome

Glucocorticoids (GCs) are associated with fragility fractures in children with various chronic illnesses. The impact of GCs on bone health in children with nephrotic syndrome (NS) is less well understood. Here we report skeletal findings in a 10-year-old boy with steroid-sensitive NS who presented with back pain due to vertebral fractures 5 years after NS diagnosis. Spine radiographs showed a Genant grade 2 fracture at T7 and a grade 1 fracture at T8. Dual-energy X-ray absorptiometry (DXA) revealed a lumbar spine areal bone mineral density (BMD) Z-score of -0.5 and a total body areal BMD Z-score of -0.4. Quantitative transiliac bone histomorphometry revealed low trabecular bone volume and cortical width but no osteomalacia. Our findings show the potential for significant bone morbidity due to osteoporosis in steroid-sensitive NS treated with intermittent GC therapy and emphasize that vertebral fractures may be an underrecognized complication. Furthermore, our report highlights that vertebral fractures can be associated with normal spine areal BMD in this context, suggesting that DXA-based, anteroposterior areal BMD should not be relied upon exclusively for assessing bone health and disease in children with steroid-sensitive NS.

Fat and bone in children: Differential effects of obesity on bone size and mass according to fracture history

Fat mass predicts bone accrual in prepubertal children, but obese children have increased fracture risk. We hypothesised that bone size and mass would vary according to prior fracture in obese children. One hundred and three children (52 obese) underwent dual-energy X-ray absorptiometry (DXA) scanning of the lumbar spine, total body, and radial metaphysis and diaphysis. We derived body size-adjusted bone mineral density (BMD) estimates for each site using commonly employed procedures. Following adjustment for either age, age(2) and weight, or height and weight based on a reference group of nonobese controls without previous fracture, obese children with prior fracture showed a 0.8 to 1.2 SD reduction in total body areal BMD (aBMD), a 3.0 SD decrease in lumbar (L2-4) aBMD, and a 2.0 SD reduction in radial shaft aBMD. These changes were significant at p < .005. Lumbar volumetric BMD (vBMD) calculated by Carter and Kröger algorithms was significantly reduced in obese children with prior fracture (2.0 to 3.3 SD). Eighteen percent of obese children fulfilled the criteria for osteoporosis. Despite greater lean mass for height in obese children (p < .0001), total body bone mineral content (BMC) for lean mass was reduced (p = .002). Multiple regression models adjusting for height, weight, and gender demonstrated an inverse relationship between total body fat mass and total body, lumbar, and ultradistal radius BMC and aBMD. The data suggest that fat mass substantially inhibits bone accrual in children with prior fracture. These children may require targeted interventions to increase bone mass during adolescence to achieve optimal peak bone mass and reduce the risk of osteoporosis later in life.

Complex genetic regulation of bone mineral density and insulin-like growth factor-I in C57BL/6J-Chr #A/J/NaJ chromosome substitution strains

Low bone mineral density (BMD) is a phenotype associated with osteoporosis and increased risk of fracture. Since 60-80% of variation in BMD is associated with genetic factors, we used the novel approach of chromosome substitution strains (CSS) to identify chromosomes that harbor genes that regulate BMD. Specifically, we evaluated 24 wk old C57BL/6J-Chr #(A/J)/NaJ CSS (n = 7 to 18) in which each chromosome in the host C57BL/6J strain is replaced by a corresponding chromosome from the donor A/J strain (19 autosomes, X, Y). We determined several A/J chromosomes contribute to body weight (BW), percent body fat (BF), whole body areal BMD (aBMD), and serum insulin-like growth factor (IGF)-I in both a positive and negative manner when compared with C57BL/6J. Specifically, C57BL/6J-Chr 5(A/J)/NaJ (B.A-5) (males) and B.A-13 (females) contributed to increased BW, whereas B.A-3, 4, 8, 9, 12, and 18 (males) and B.A-3, 4, and 11 (females) contributed to reduced BW. B.A-5 (males) and B.A-13 (females) contributed to increased BF, whereas B.A-12 (males) and B.A-3, 4, 10, and 11 (females) contributed to reduced BF. B.A-14 (females) contributed to increased aBMD and B.A-1, 2, 6, 9, 10, and 18 (males) and B.A-8, 9, and 10 (females) contributed to reduced aBMD. To determine if similar chromosomes regulate aBMD and IGF-I, we determined serum concentrations of IGF-I. B.A-14 and Y (males) and B.A-6 (females) contributed to increased IGF-I and male B.A-3 and female B.A-8 contributed to reduced IGF-I. Overall, we identified several sex-dependent and -independent chromosomes that regulate aBMD and IGF-I in adult mice.

Chemical mutagenesis induced two high bone density mouse mutants map to a concordant distal chromosome 4 locus

Phenotype-driven mutagenesis approach in the mouse holds much promise as a method for revealing gene function. Earlier, we have described an N-ethyl- N-nitrosourea (ENU) mutagenesis screen to create genome-wide dominant mutations in the mouse model. Using this approach, we describe identification of two high bone density mutants in C57BL/6J (B6) background. The mutants, named as 12184 and 12137, have been bred more than five generations with wild-type B6 mice, each producing > 200 backcross progeny. The average total body areal bone mineral density (aBMD) was 13–17% higher in backcrossed progeny from both mutant lines between 6 and 10 weeks of age, as compared to wild-type (WT) B6 mice ( n = 60–107). At 3 weeks of age the aBMD of mutant progeny was not significantly affected as compared to WT B6 mice. Data from 10- and 16-week old progeny show that increased aBMD was mainly related to a 14–20% higher bone mineral content, whereas bone size was marginally increased. In addition, the average volumetric BMD (vBMD) was 5–15% higher at the midshaft tibia or femur, as compared to WT mice. Histomorphometric analysis revealed that bone resorption was 23–34% reduced in both mutant mice. Consistent with histomorphometry data, the mRNA expression of genes that regulate osteoclast differentiation and survival were altered in the 12137 mutant mice. To determine the chromosomal location of the ENU mutation, we intercrossed both mutant lines with C3H/HeJ (C3H) mice to generate B6C3H F2 mice ( n = 164 for line 12137 and n = 137 F2 for line 12184). Interval mapping using 60 microsatellite markers and aBMD phenotype revealed only one significant or suggestive linkage on chromosome 4. Since body weight was significantly higher in mutant lines, we also used body weight as additive and interactive covariate for interval mapping; both analyses showed higher LOD scores for both 12137 and 12184 mutants without affecting the chromosomal location. The large phenotype in the mutant mice compared to generally observed QTL effects (< 5%) would increase the probability of identifying the mutant gene.

Intravenous pamidronate treatment of children under 36 months of age with osteogenesis imperfecta

Introduction Bone mineral density (BMD) and fracture rates in children with osteogenesis imperfecta (OI) have been shown to improve with bisphosphonate therapy. There are limited data available on the efficacy of this therapy in children with OI under the age of 3 years. To examine this, we instituted a prospective clinical trial of intravenous bisphosphonate to study safety, feasibility, and efficacy of this therapy. Materials and methods Nine infants and young children with osteogenesis imperfecta (age range 1–35 months) were treated with intravenous pamidronate. Six had type II OI, two had type I, and one had type IV. Pamidronate was administered in cycles of 3 consecutive days. The total duration of therapy ranged from 11 to 29 months (mean 17 months). Results During treatment, the mean annualized percent change in total body areal BMD was 25% (range 11–40%). Pamidronate therapy resulted in sustained and significant decreases in serum calcium and bone-specific alkaline phosphatase and in urine calcium/creatinine and NTX/creatinine. Fracture rate in the group decreased from 80 fractures in 111 months before treatment to 25 fractures in 152 months after treatment ( P < 0.01). Linear growth and weight gain were maintained. Other than fevers in several infants following the initial dose of intravenous bisphosphonate no adverse effects of therapy were noted. Conclusions Our data support that intravenous pamidronate therapy is safe, increases BMD, and reduces fracture rates in very young children with OI. Currently, it would seem to be the best available treatment for these children.

Effect of diet-induced weight loss on total body bone mass.

1. Total body areal bone mineral density was measured by dual-energy X-ray absorptiometry in eight women before and 10 weeks after a very-low-calorie diet [405 kcal (1701 kJ)/day]. 2. The mean weight loss of 15.6 kg was accompanied by a statistically significant reduction in total body bone mineral density from 1.205 +/- 0.056 to 1.175 +/- 0.058 g/cm2 (mean +/- SD, P less than 0.005). 3. After cessation of the diet, weight gradually increased and by 10 months was similar to baseline values. Total body bone mineral density also increased after stopping the diet and mean values obtained 10 months after the diet did not differ significantly from initial values. Throughout the study total body bone mineral density values in all subjects were well within the range reported for normal subjects. 4. These data indicate that diet-induced weight loss is associated with rapid bone loss, subsequent weight gain being accompanied by increases in bone mass. Further studies are required to establish the clinical significance of these findings and, in particular, the skeletal distribution of bone loss.