Lower Vertebral Bone Mineral Density Research Articles

P114. The role of lumbosacral paraspinal muscle degeneration and low vertebral bone mineral density on distal instrumentation-related problems following long spinal fusion for degenerative lumbar scoliosis: a retrospective cohort study

P114. The role of lumbosacral paraspinal muscle degeneration and low vertebral bone mineral density on distal instrumentation-related problems following long spinal fusion for degenerative lumbar scoliosis: a retrospective cohort study

The role of lumbosacral paraspinal muscle degeneration and low vertebral bone mineral density on distal instrumentation-related problems following long-instrumented spinal fusion for degenerative lumbar scoliosis: a retrospective cohort study.

This study aimed to confirm the role of paraspinal muscle degeneration and low vertebral bone mineral density (vBMD) of the lumbosacral region in the development of distal instrumentation-related problems (DIPs) in degenerative lumbar scoliosis (DLS) patients undergoing long-instrumented spinal fusion. From 2013 to 2019, 125 DLS patients with 24-month follow-up after long-instrumented spinal fusion in Beijing Chao-Yang Hospital were retrospectively recruited and divided into DIP and non-DIP groups. Demographic characteristics, surgical data, and radiographic parameters were statistically compared between the groups. Degeneration of the paraspinal muscle was evaluated using the relative gross cross-sectional area (rGCSA), relative functional cross-sectional area (rFCSA), ratio of the rFCSA to rGCSA, gross muscle-fat index, and functional muscle-fat index of the multifidus (MF), erector spinae (ES), paraspinal extensor muscle (PSE), and psoas major determined by preoperative magnetic resonance imaging (MRI). The vBMD of the lumbosacral region and lower instrumented vertebra (LIV) was assessed using Hounsfield unit (HU) values determined by computed tomography (CT) scans. The DeLong test was performed to select MRI and CT scan variables. Multivariable logistic regression analysis was applied to determine the independent predictive factors of DIPs. The incidence of DIPs was 16.0% (20/105). There were no significant differences in demographic characteristics or surgical data between the groups. The rFCSAs of the MF (65.74±21.51 vs. 92.37±21.68; P<0.001), ES (82.67±21.44 vs. 111.48±24.21; P<0.001) and PSE (144.31±36.12 vs. 208.48±41.57; P<0.001) and the HU values of the lumbosacral region (103.80±22.64 vs.. 132.19±19.17; P<0.001) and LIV (111.70±23.23 vs. 128.69±20.70; P=0.005) were significantly lower in the DIP group. Significantly less preoperative pelvic tilt and greater postoperative lumbosacral lordosis and sagittal vertical axis (SVA) values were observed in the DIP group. The rFCSA of the PSE, the HU value of the lumbosacral region, and the postoperative SVA value were detected as independent predictive factors of DIPs. Lower muscularity of the PSE, a lower vBMD of the lumbosacral region, and postoperative sagittal malalignment were independent predictive factors of DIPs. Surgeons should emphasize the preoperative evaluation of paraspinal muscle and bone mass in DLS patients.

No relationship between bone mineral density and syndesmophyte formation at the same level in the lumbar spine of patients with radiographic axial Spondyloarthritis

ObjectiveTo investigate if in radiographic axial Spondyloarthritis (r-axSpA) low vertebral bone mineral density (BMD) is associated with development of new syndesmophytes at the same vertebral level.MethodsIn a post-hoc analysis from...

SAT-LB68 A Rare De Novo Mutation in LRP5 Gene in an Adolescent Female With Juvenile Onset Primary Osteoporosis

Background: Juvenile onset of primary osteoporosis is a rare skeletal disorder with a highly heterogenous clinical presentation and complex poorly understood genetic etiology. Low-density lipoprotein receptor-related protein 5 (LRP5), a Wnt-β-catenin pathway receptor involved in bone mineral density (BMD) regulation, has been reported in children with primary osteoporosis mainly due to missense and frame-shift mutations. To our knowledge, there is only one report of in-frame deletions in exon 21 possibly being implicated in pregnancy related osteoporosis (1). We report the first case of a rare heterozygous de novo in-frame deletion in exon 21 of LRP5 gene in a girl with juvenile onset primary osteoporosis. Clinical Case: A 7.5 yo previously healthy European-African-American female born to non-consanguineous family, was noted to have left ankle and bilateral wrists fractures during sport activities occurring over the span of 1 y. On exam, she was of normal stature, had normal sclerae and vision, but was found to have hypermobile joints. Initial blood work revealed an elevated iPTH 72 pg/mL (9-59), normal Ca 9.6 mg/dL (8.9-10.4), and low 25OH-Vitamin D 17 ng/mL (30-100), which normalized with supplementation to 30.4 ng/mL. By 10.5 yo, she had sustained multiple sports related and pathologic fractures of long bones with progressive bone pain and functional ambulatory impairment. Radiographic evaluation showed osteopenia, multiple healed long bone fractures with presumed non-ossifying fibroma in the distal right femoral metaphysis, and subtle height loss of T4-5 vertebrae. CT bone densitometry at 12 yo showed low mean cancellous lumbar vertebral BMD of 190 mg/cm3 (ref. 285 ± 45) and normal cortical BMD of the femoral midshaft of 1977 mg/cm3 (ref. 2000 ± 60). Genetic testing for Osteogenesis Imperfecta returned negative for COL1A1 and COL1A2 mutations. Whole exome sequencing (WES) revealed a rare, de novo heterozygous mutation in exon 21 that involved deletion of nucleotides 4454 to 4465 resulting in an in-frame deletion of amino acid 1485 to 1488. This mutation is predicted to be deleterious by in silico analysis. Conclusion: We present the first case of a young female with progressive pathologic fractures, functional ambulatory impairment, and low BMD in childhood, consistent with juvenile onset primary osteoporosis. WES revealed a rare de novo heterozygous in-frame deletion mutation in LRP5, providing a plausible biological mechanism for her clinical presentation, and further contributing to the increasing genetic heterogeneity of juvenile onset primary osteoporosis and LRP5-related bone disorders. Reference: (1) Cook, F., Mumm, S., Whyte, M., Wenkert, D. Pregnancy-associated osteoporosis with a heterozygous deactivating LDL receptor-related protein 5 (LRP5) mutation and a homozygous methylenetetrahydrofolate reductase (MTHRF) polymorphism. JBMR. 2014;29 (4): 922-8.

Low bone mineral density of vertebral lateral projections can predict spinal radiographic damage in patients with ankylosing spondylitis.

To investigate the association between bone mineral status and spinal radiographic damage in patients with ankylosing spondylitis (AS) and determine whether bone mineral status can predict further spinal radiographic damage after 2years. Bone mineral density (BMD) of the lumbar spine (anteroposterior and lateral projections), femoral neck, and total hip and trabecular bone score (TBS) of the lumbar spine were measured in AS patients (n = 54) who fulfilled the modified New York criteria. Spinal radiographic damage was scored on cervical and lumbar spine radiographs using modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) at baseline and after 2years. Simple and multiple linear regression analyses were performed to examine predictors of spinal radiographic damage. Patients with advanced AS exhibited low BMD on lumbar spine lateral projections, femoral neck, and total hip and low TBS. Low vertebral bone mass at baseline, assessed by BMD of the lateral projections or TBS, was independently associated with baseline mSASSS. After 2years, mSASSS change from baseline was significantly associated with high baseline mSASSS, high baseline erythrocyte sedimentation rate and C-reactive protein (CRP) levels, and low baseline BMD of the lumbar spine lateral projections. The best predictive model for spinal radiographic progression consisted of baseline mSASSS, baseline CRP, and low BMD of lateral lumbar spine (area under curve = 0.826). BMD at vertebral lateral projections and TBS were inversely associated with baseline mSASSS in AS patients. Low BMD at vertebral lateral projections, as well as baseline mSASSS and inflammatory markers, might predict spinal radiographic damage in AS.Key Points• Vertebral bone mineral density of lateral projections and trabecular bone score are inversely associated with baseline mSASSS in patients with ankylosing spondylitis.• Baseline mSASSS, inflammatory markers, and low vertebral bone mineral density might predict spinal radiographic progression in patients with ankylosing spondylitis.

CT-Based Diagnosis of Low Vertebral Bone Mineral Density Is Associated with Hypercalciuria and Hypocitraturia on Opportunistic Imaging

Studies have demonstrated associations between nephrolithiasis and systemic conditions, including low bone mineral density (BMD), which may correlate with hypercalciuria in kidney stone formers (KSFs). Traditionally, low BMD is diagnosed with dual-energy X-ray absorptiometry. As a noncontrast CT (NCCT) scan is typically part of a stone evaluation, our objective was to evaluate the association of NCCT-based vertebral BMD with 24-hour urine parameters in KSF. This is a retrospective analysis of 99 KSFs who had CT imaging and 24-hour urine studies. For each patient, BMD was estimated at the L1 vertebral body and CT attenuation measured in HU. A threshold of 160 HU was chosen to distinguish normal from low BMD. Univariate and multivariate logistic regression analysis was performed to compare patients with low and normal BMD. Multivariate linear regression was performed to assess for variables associated with 24-hour urine parameters. Patients with low BMD had higher 24-hour urine calcium (219 vs 147 mg/day, p < 0.0001) and larger stone volume (259 vs 78.4 mm3, p = 0.009). Multivariate analysis demonstrated age >60 years (odds ratio [OR] 9.3, p < 0.0001) and hypercalciuria (OR 4.34, p = 0.004) correlated with low BMD. Linear regression demonstrated that lower BMD was associated with higher urinary calcium (β-coefficient -0.268, p = 0.009) and lower urinary citrate (β-coefficient 0.332, p = 0.01). CT-based diagnosis of low mineral bone density is associated with derangement in 24-hour urine calcium and citrate in KSFs, as well as larger stone volumes.

RANK-RANKL Mediated Bone Destruction in B-Cell Acute Lymphoblastic Leukemia

Survival rates for pediatric B-Cell Acute Lymphoblastic Leukemia (B-ALL) have improved dramatically over the past 40 years approaching a current long-term survival rate of 85%. However childhood B-ALL patients continue to confront co-morbidities and their long-term consequences. For example, osteopenia and osteoporosis associated fractures are a common complication of pediatric leukemia at diagnosis, during treatment and in long-term B-ALL survivors. The STeroid-associated Osteoporosis in the Pediatric Population (STOPP) study reported that at ALL diagnosis, 16% of children and adolescents present with bone pain, vertebral compression and low vertebral Bone Mineral Density (BMD) scores, with the greatest incidence of vertebral fractures (VF) seen in the first year following diagnosis (J Clin Endocrinol Metab. 2015, 100:3408-17). Glucocorticoid treatment further elevated fracture risk in this population. These data underscore the need to identify molecular mechanism by which leukemic cells contribute to bone loss, and provide targeted therapies to limit these effects.Our laboratory previously showed that Rag2-/- p53-/- Prkdcscid/scid triple mutant (TM) and p53-/- Prkdcscid/scid double mutant (DM) mice develop spontaneous B-ALL, but only TM animals exhibit dissemination of leukemic blasts to the leptomeninges of the CNS, a poor prognosis feature observed in pediatric and adult ALL patients. We observed that TM leukemic mice also displayed fragile vertebral bones. Using comparative transcriptome analysis, we found that RANKL (Receptor Activator of the Nuclear factor-kB Ligand), a Tumor Necrosis Factor (TNF) superfamily member ligand and a key regulator of B cell and osteoclast differentiation, was expressed at greater levels in TM compared to the DM leukemia cells. RANKL binds to its receptor RANK, which is expressed in osteoclast precursor cells. RANK-RANKL interaction induces signaling in the osteoclast precursors and drives their differentiation into mature bone resorbing osteoclasts (Proc. Natl. Acad. Sci. 1999, 96:3540-3545). Upon adoptive leukemia cell transfer into immune deficient mice, RANKL+ TM but not DM cells caused decreased vertebral trabecular bone density in the recipients. Treatment with the recombinant RANKL antagonist protein Osteoprotegerin (OPG-Fc) inhibited the growth and dissemination of RANKL+TM leukemic cells and attenuated bone destruction in the recipient mice. These data suggested that TM mouse leukemia cells cause bone loss in the absence of glucocorticoid or other chemotherapy agents.We then examined the potential role of RANKL in osteoporosis associated with human B-ALL. RANKL mRNA was expressed by a majority of primary human adult and pediatric B-ALL. To determine whether primary patient B-ALL can cause bone loss, we transplanted RANKL+ human B-ALL samples of multiple cytogenetic high-risk subgroups (Complex, hypo-diploid and Mixed Lineage Leukemia (MLL) rearranged) into NOD.SCID.gC-/-(NSG) recipient mice. Micro-CT imaging and bone density measures in the xenotransplant recipients revealed extensive vertebral trabecular bone destruction. Immuno-histological analysis of the human B-ALL recipient mice demonstrated extensive osteoporotic damage of the long bones and marked RANKL protein expression in the long bones of mice harboring extensive human B-ALL cell burden compared to NSG control mice. To determine whether RANKL-RANK interaction was required for the B-ALL mediated bone destruction, cohorts of NSG mice engrafted with human B-ALL were treated with recombinant OPG-Fc compared to a matched Fc control protein. OPG-Fc treatment did not attenuate leukemia cell expansion and bone marrow burden, but despite bulky disease, the treatment conferred robust protection from bone destruction suggesting that RANKL was a critical mediator of this clinical complication.Our data demonstrate a central role of the RANK-RANKL axis in B-ALL-mediated bone disease and identify an actionable therapeutic target to reduce acute and long-term morbidity. Denosumab, an anti-RANKL antibody has been approved for the treatment of bone metastasis by solid tumors and for post-menopausal osteoporosis. Our pre-clinical studies suggest that Denosumab and other agents that inhibit the RANK-RANKL pathway may be efficacious in patients with B-ALL associated bone degeneration. DisclosuresNo relevant conflicts of interest to declare.

ASSOCIATION BETWEEN LOW BONE MINERAL DENSITY, METABOLIC SYNDROME AND SEX STEROIDS DEFICIENCY IN MEN.

To analyze the association between low bone mineral density (BMD), metabolic syndrome (MS) and sex hormones deficiency in men. We included in this retrospective study 199 men with osteoporosis or osteopenia and 167 men with normal BMD as controls, aged between 55-85 years old. Patients' evaluation included: medical history and physical examination, X-ray of thoracic and lumbar spine, measuring BMD at hip and lumbar spine, serum glucose and lipid profile, serum levels of total testosterone (tT), free testosterone (fT) and estradiol (E2). The results revealed a significant association between low BMD and MS (p=0.011). Vertebral fractures were more frequently associated with MS (p=0.041). Patients with MS had lower vertebral BMD (p=0.037) and lower E2 levels (p=0.024) compared with those without MS. In men with MS, E2 deficiency can predict the value of vertebral and hip BMD. fT deficiency can predict only the value of hip BMD. A significant association between MS, low BMD, vertebral fractures and sex steroids deficiency, in particular E2 and fT was found. The presence of MS and sex hormones deficit can predict the reduction of BMD.

Bone three-dimensional microstructural features of the common osteoporotic fracture sites.

Osteoporosis is a common metabolic skeletal disorder characterized by decreased bone mass and deteriorated bone structure, leading to increased susceptibility to fractures. With aging population, osteoporotic fractures are of global health and socioeconomic importance. The three-dimensional microstructural information of the common osteoporosis-related fracture sites, including vertebra, femoral neck and distal radius, is a key for fully understanding osteoporosis pathogenesis and predicting the fracture risk. Low vertebral bone mineral density (BMD) is correlated with increased fracture of the spine. Vertebral BMD decreases from cervical to lumbar spine, with the lowest BMD at the third lumbar vertebra. Trabecular bone mass of the vertebrae is much lower than that of the peripheral bone. Cancellous bone of the vertebral body has a complex heterogeneous three-dimensional microstructure, with lower bone volume in the central and anterior superior regions. Trabecular bone quality is a key element to maintain the vertebral strength. The increased fragility of osteoporotic femoral neck is attributed to low cancellous bone volume and high compact porosity. Compared with age-matched controls, increased cortical porosity is observed at the femoral neck in osteoporotic fracture patients. Distal radius demonstrates spatial inhomogeneous characteristic in cortical microstructure. The medial region of the distal radius displays the highest cortical porosity compared with the lateral, anterior and posterior regions. Bone strength of the distal radius is mainly determined by cortical porosity, which deteriorates with advancing age.

Effect of Rosiglitazone on Bone Quality in a Rat Model of Insulin Resistance and Osteoporosis

OBJECTIVERosiglitazone (RSG) is an insulin-sensitizing drug used to treat type 2 diabetes mellitus. The A Diabetes Outcome Progression Trial (ADOPT) shows that women taking RSG experienced more fractures than patients taking other type 2 diabetes drugs. These were not osteoporotic vertebral fractures but, rather, occurred in the limbs. The purpose of this study was to investigate how RSG treatment alters bone quality, which leads to fracture risk, using the Zucker fatty rat as a model.RESEARCH DESIGN AND METHODSA total of 61 female 4-month-old rats were divided into six groups. One Sham group was a control and another was administered oral RSG 10 mg/kg/day. Four ovariectomized (OVX) groups were dosed as follows: controls, RSG 10 mg/kg, alendronate (ALN, injected at 0.7 mg/kg/week), and RSG 10 mg/kg plus ALN. After 12 weeks of treatment, bone quality was evaluated by mechanical testing. Microarchitecture, bone mineral density (BMD), cortical bone porosity, and bone remodeling were also measured.RESULTSOVX RSG 10 mg/kg rats had lower vertebral BMD and compromised trabecular architecture versus OVX controls. Increased cortical bone porosity and decreased mechanical properties occurred in these rats. ALN treatment prevented decreased BMD and architectural and mechanical properties in the OVX model. Reduced bone formation, increased marrow adiposity, and excess bone resorption were observed in RSG-treated rats.CONCLUSIONSRSG decreases bone quality. An unusual finding was an increase in cortical bone porosity induced by RSG, consistent with its effect on long bones of women. ALN, an inhibitor of bone resorption, enhanced mechanical strength and may provide an approach to partially counter the deleterious skeletal effects of RSG.

ApoE−/−Fas−/− C57BL/6 mice: a novel murine model simultaneously exhibits lupus nephritis, atherosclerosis, and osteopenia

To establish a mouse model of accelerated atherosclerosis in lupus, we generated apolipoprotein E-deficient (apoE(-/-)) and Fas(lpr/lpr) (Fas(-/-)) C57BL/6 mice. On a normal chow diet, 5 month old apoE(-/-)Fas(-/-) mice had enlarged glomerular tuft areas, severe proteinuria, increased circulating autoantibody levels, and increased apoptotic cells in renal and vascular lesions compared with either single knockout mice. Also, double knockout mice developed increased atherosclerotic lesions but decreased serum levels of total and non-HDL cholesterol compared with apoE(-/-)Fas(+/+) littermates. Moreover, female apoE(-/-)Fas(-/-) mice had lower vertebral bone mineral density (BMD) and bone volume density (BV/TV) than age-matched female apoE(-/-)Fas(+/+) mice. Compared with apoE(-/-)Fas(+/+) and apoE(+/+)Fas(-/-) mice, apoE(-/-)Fas(-/-) mice had decreased circulating oxidized phospholipid (OxPL) content on apoB-100 containing lipoprotein particles and increased serum IgG antibodies to OxPL, which were significantly correlated with aortic lesion areas (r = 0.58), glomerular tuft areas (r = 0.87), BMD (r = -0.57), and BV/TV (r = -0.72). These results suggest that the apoE(-/-)Fas(-/-) mouse model might be used to study atherosclerosis and osteopenia in lupus. Correlations of IgG anti-OxPL with lupus-like disease, atherosclerosis, and bone loss suggested a shared pathway of these disease processes.

Risk of vertebral osteoporosis in post-menopausal women with alterations of the mandible

Previous studies have suggested that a thin or eroded cortex of the mandible detected on dental panoramic radiographs is associated with low vertebral bone mineral density (BMD) or osteoporosis. However, those studies did not estimate the multivariate-adjusted risk for low vertebral BMD or osteoporosis associated with alterations of the mandible. BMD of the lumbar vertebrae (L2-L4) was compared among quartiles of cortical width and among three cortical shape categories in 450 post-menopausal women (mean age, 57.2 years), adjusted for potential confounders. The odds ratios for low BMD or osteoporosis according to cortical width and shape were also calculated. Significant associations were found between cortical width and shape, and vertebral BMD. The odds ratios for low vertebral BMD associated with the second, third and lowermost quartiles of cortical width were 1.71 (95% confidence interval (CI), 0.96-3.05), 2.30 (95% CI, 1.29-4.11) and 5.43 (95% CI, 2.16-10.71), respectively, compared with the uppermost quartile. The odds ratios for osteoporosis according to cortical width category were similar to those for low BMD. The odds ratios for low BMD associated with mildly to moderately and severely eroded cortices were 3.85 (95% CI, 2.37-6.25) and 7.84 (95% CI, 2.57-23.90), respectively, compared with normal cortex. The odds ratios for osteoporosis associated with mildly to moderately and severely eroded cortices were 4.73 (95% CI, 2.54-8.80) and 14.73 (95% CI, 6.14-35.47), respectively. Post-menopausal women with alterations of the mandible may have an increased risk for low vertebral BMD or osteoporosis.

Mechanical efficacy of vertebroplasty: Influence of cement type, BMD, fracture severity, and disc degeneration

Introduction Osteoporotic vertebral fractures can be treated by injecting bone cement into the damaged vertebral body. “Vertebroplasty” is becoming popular but the procedure has yet to be optimised. This study compared the ability of two different types of cement to restore the spine's mechanical properties following fracture, and it examined how the mechanical efficacy of vertebroplasty depends on bone mineral density (BMD), fracture severity, and disc degeneration. Methods A pair of thoracolumbar “motion-segments” (two adjacent vertebrae with intervening soft tissue) was obtained from each of 15 cadavers, aged 51–91 years. Specimens were loaded to induce vertebral fracture; then one of each pair underwent vertebroplasty with polymethylmethacrylate (PMMA) cement, the other with another composite material (Cortoss). Specimens were creep loaded for 2 h to allow consolidation. At each stage of the experiment, motion segment stiffness in bending and compression was measured, and the distribution of compressive loading on the vertebrae was investigated by pulling a miniature pressure transducer through the intervertebral disc. Pressure measurements, repeated in flexed and extended postures, indicated the intradiscal pressure (IDP) and neural arch compressive load-bearing (F N). BMD was measured using DXA. Fracture severity was quantified from height loss. Results Vertebral fracture reduced motion segment stiffness in bending and compression, by 31% and 43% respectively ( p < 0.001). IDP fell by 43–62%, depending on posture ( p < 0.001), whereas F N increased from 14% to 37% of the applied load in flexion, and from 39% to 61% in extension ( p < 0.001). Vertebroplasty partially reversed all these effects, and the restoration of load-sharing was usually sustained after creep-consolidation. No differences were observed between PMMA and Cortoss. Pooled results from 30 specimens showed that low BMD was associated with increased fracture severity (in terms of height loss) and with greater changes in stiffness and load-sharing following fracture. Specimens with low BMD and more severe fractures also showed the greatest mechanical changes following vertebroplasty. Conclusions Low vertebral BMD leads to greater changes in stiffness and spinal load-sharing following fracture. Restoration of mechanical function following vertebroplasty is little influenced by cement type but may be greater in people with low BMD who suffer more severe fractures.

Treatment With a Luteinizing Hormone-Releasing Hormone Agonist in Adolescents With Short Stature

When children with precocious puberty dependent on luteinizing hormone-releasing hormone (LHRH) are given an LHRH agonist, their adult height is augmented. Some clinicians prescribe this treatment to increase height in short adolescents. This randomized trial sought to determine whether treatment with an LHRH agonist increases adult height in short adolescents with normally timed puberty. The hypothesis tested was that a 4-year course of treatment would increase adult height by delaying senescence of the growth plate, thereby prolonging the time during which linear growth takes place. Participating were 50 adolescents, 32 girls and 18 boys, whose predicted adult height was at least 2.25 standard deviations (SD) below the population mean (average, 33 ′ 1.2 SD). In all cases, the hand and wrist epiphyses were unfused. Using a double-blind design, 26 subjects received the LHRH agonist deslorelin in a dose of 4 μg/kg given each evening by subcutaneous injection for a mean of 3.5 years. The remaining 24 subjects received a placebo for a mean of 2.1 years. Adult height was measured when bone age was greater than 16 years in girls, or 17 years in boys, and when the growth rate was less than 1.5 cm per year. All participants had midpubertal peak LH responses to LHRH at the outset. LHRH-stimulated levels of both LH and follicle-stimulating hormone declined during agonist therapy. When adult height was reached, those given agonist therapy were older than placebo recipients (20.5 vs. 18 years) and were also taller. Treatment increased the SD score for height by 0.6 (95% confidence interval [CI], 0.2-0.9). Height was 4.2 cm greater on average (95% CI, 1.7-6.7) than the initially predicted adult height. Adult height was significantly greater in subjects given LHRH than in those receiving placebo. This was true both for adolescents with idiopathic short stature and those with a growth-limiting syndrome. Bone age increased less in actively treated subjects than in the placebo group, but there was no significant difference at the time adult height was reached. At adult height, those given agonist therapy had lower vertebral bone mineral density at the time of adult height than did placebo recipients. Educational achievement was comparable in the 2 groups. Treatment did not appear to influence secondary sexual development. These findings affirm the value of LHRH agonist treatment for moderately increasing adult height in short adolescents without precocious puberty. The major side effect is a decrease in bone mineral density. In most cases the potential benefit of agonist therapy will not outweigh the risks, and the investigators do not recommend its routine use in these adolescents.

Osteoporosis after renal transplantation: single center experience.

Osteoporosis is a major source of morbidity after renal transplantation. The aim of this retrospective study was to determine the independent influences of different parameters on bone mineral density (BMD) in various parts of the body after renal transplantation. BMD was measured in 130 of 954 renal allograft recipients who underwent surgery between 1985 and 1999. Time since transplantation and cumulative prednisolone doses were significantly higher in patients who had osteoporosis of the lumbar vertebrae (P=0.06 and 0.034, respectively). Logistic regression analysis revealed that cumulative prednisolone dose was the only significant predictor of low vertebral BMD (P=0.02, r=0.33). For the neck of the femur, high blood urea nitrogen and low Mg levels were found to be the predictors of low bone density (P=0.002 and 0.04, respectively). Although parathyroid hormone levels were higher in femoral osteoporosis patients than in those not affected at this site, the difference was not statistically significant (P=0.294). Time since transplantation, cumulative prednisolone dose, and cyclosporine A dose were all found to have a major negative impact on BMD in the radius region (P=0.001, 0.000, 0.001, respectively). Regression analysis showed that cumulative prednisolone dose (P=0.0008, r=0.34), time since transplantation (P=0.005, r=0.27), body mass index (P=0.01, r=-0.21), male gender (P=0.02, r=-0.21), and age (P=0.04, r=0.16) all had major effects on radius BMD. In conclusion, the radius seems to be one of the major parts of the skeleton affected by factors introduced after renal transplantation.

AGE-INDEPENDENT CORRELATION OF OPTICALLY DETERMINED THORACIC KYPHOSIS WITH LUMBAR SPINE BONE MINERAL DENSITY

The thoracic spine is susceptible to age-related increases in the sagittal curve, a process which is accentuated in osteoporosis. Previous studies have demonstrated an association between low vertebral bone mineral density (BMD) and accentuation of kyphosis. However, concerns of ionizing radiation associated with radiographic evaluation of osteoporotic fracture risks create a demand for alternative noninvasive detection methods. Back shape, and in particular the thoracic kyphosis, may act as a surrogate for bone density and complement methods of screening individuals for osteoporosis or monitoring progression. The aim of this prospective study is to establish the statistical association of mean lumbar spine BMD and the age-independent BMD Z-score with kyphosis, measured from noninvasive, rasterstereographic analysis of back shape. Back shape imaging of 42 females was performed following routine lumbar bone densitometry using dual energy X-ray absorptiometry. Kyphosis parameters derived from an optical back shape imaging system were correlated, using simple linear regression models, against mean lumbar BMD and BMD Z-scores. Moderate associations were noted between lumbar BMD and thoracic kyphosis (r=0.63 to 0.71, p&lt;0.0001). The trend was still evident when correlating kyphosis against BMD Z-scores (r=0.57 to 0.68, p&lt;0.0001). These data confirm earlier studies comparing radiographic indices of thoracic curvature with vertebral BMD, and suggest potential application of noninvasive back shape imaging to assist in the screening of individuals at risk of spinal osteoporosis, particularly in younger populations.

Consensus Summary on the Diagnosis and Treatment of Osteoporosis

Consensus Summary on the Diagnosis and Treatment of Osteoporosis

Evaluation of quantitative CT vertebral bone mineral density measurement and the Singh index in elderly females with hip fractures--a case control study.

This study aims to evaluate the ability of quantitative computed tomography (QCT) bone mineral density (BMD) measurement of vertebral bodies to predict risk of hip fracture. We also examine the predictive value of the radiographic Singh index and its relationship to the vertebral BMD. The vertebral BMD (using a QCT protocol) and radiographic Singh index were evaluated in 86 white females who had sustained a hip fracture after minor trauma. 86 age-matched female controls were also studied. All patients were post-menopausal, the age range was 52-95 years. BMD values were found to be low in both the study group and controls; there was no statistically significant difference between the groups. A low Singh index did not correlate with hip fracture, nor did it correlate with low vertebral BMD measurement. We conclude that vertebral BMD and radiographic Singh index are not reliable predictors of hip fracture in the elderly female.

Physical exercise and the skeleton

The skeleton provides more than only a framework for the body. Bone is a calcified conjunctive tissue sensitive to various mechanical stimuli, mainly to those resulting from gravity and muscular contractions. Numerous animal and human studies demonstrate the importance of weight-bearing physical activity as well as mechanical loading for maintaining skeletal integrity. Lack of weight-bearing activity is dangerous for the skeleton: a decrease in bone mineral density (BMD) has been demonstrated in animals and humans under conditions of weightlessness or immobilization. Other studies have also reported a lower vertebral BMD among young amenorrheic athletes than among athletes with regular cycles and/or non athletes. The main factor responsible for this lower BMD in the amenorrheic athletes is the persistent low level of endogenous estrogen observed among these women. However this does not represent a premature and irreversible loss of bone mass since the resumption of menses following a decrease in training is the primary factor for a significant increase in vertebral BMD in these formerly amenorrheic athletes. A weight-bearing exercise is likely to be more beneficial at weight-bearing than at non weight-bearing sites, and hypogonadism resulting from very intensive training and exercise is more detrimental to trabecular than cortical bone. Bone deficit at non weight-bearing sites may be attenuated by maintenance of body weight. Nevertheless the etiology of "stress fractures" among athletes remains poorly understood, and the exact relationship between soft tissue mass and BMD is not clear. Osteoporosis, the most common bone disorder in France, is a pathological condition associated with increased loss of bone mass, resulting in a greater risk of fracture. Although symptoms of osteoporosis do not generally occur until after menopause, recent evidence suggests that bone loss starts much earlier in life. Therefore osteoporosis might be prevented by increasing peak bone mass and/or by slowering bone loss after menopause. Exercise such as resistance training or weight-bearing activities like running or walking have an osteogenic effect on increasing BMD in young people, and the decrease in BMD is slower in exercised than in non-exercised post-menopausal women. Nevertheless the influence of the length and of the intensity of such physical activities remain to be determined.

Influence of early age at menopause on vertebral bone mass

Menopause leads to rapid bone loss, mainly as a result of estrogen deficiency superimposed on the age-related linear bone loss. The influence of age at menopause on bone loss is unclear, although early menopause is widely considered a risk factor for osteoporosis. Vertebral bone mineral density (BMD) was measured in 1667 women divided into five groups according to hormonal status and age at menopause. Menopausal status was an independent predictor of BMD in a multiregression analysis, along with current age, years since menopause (YSM), weight, and height. For the same chronologic age (55 years), women with early menopause had a 15% lower BMD and a higher YSM than women whose menopause occurred later ("normal" menopause). After adjusting for the interval since menopause, postmenopausal women with early menopause were found to have lower vertebral BMD than postmenopausal women with normal menopause. Finally, after the age of 60, 66% of the women with early menopause had a BMD that was below the fracture threshold compared to 18% of the women with normal menopause. The results of this cross-sectional study suggest that early menopause is associated with a quantitatively higher bone loss than in women with menopause of later onset and thus constitutes a risk factor for osteoporosis.