Mean Lumbar Spine Bone Mineral Research Articles

Effectiveness and safety of pamidronate treatment in nonambulatory children with low bone mineral density.

Nonambulatory pediatric patients may have low bone mineral density (BMD) and increased risk of pathologic fractures. Though bisphosphonate therapy is the mainstream medical intervention in these children, clinical data regarding this treatment are limited. Therefore, this study aimed to evaluate the effectiveness and safety of bisphosphonate therapy in such children. We conducted a retrospective study of 21 nonambulatory children (Gross Motor Function Classification System level V) with BMD z-score ≤ -2.0 who were treated with intravenous pamidronate for at least 1 year. These patients received pamidronate every 4 months at a dose of 1.0 to 3.0 mg/kg for each cycle and had regular follow-ups for at least 1 year. The main outcome measures were changes in BMD, risk rate of fracture, biochemical data, and adverse events. The average duration of pamidronate treatment was 2.0±0.9 years, and the mean cumulative dose of pamidronate according to body weight was 7.7±2.5 mg/kg/yr. After treatment, the mean lumbar spine bone mineral content, BMD, and height-for-age-z-score-adjusted BMD z-score (BMDhazZ) significantly improved. The relative risk of fracture after treatment was 0.21 (p=0.0032), suggesting that pamidronate treatment reduced fracture incidence significantly. The increase in the average dose per body weight in each cycle significantly increased the changes in BMDhazZ. Pamidronate treatment improved the bone health of nonambulatory children with low bone density without any significant adverse events. Independent of cumulative dosage and duration of treatment, the effectiveness of pamidronate increased significantly with an increase in the average dose per body weight in subsequent cycles.

PSAT157 Efficacy of Bisphosphanate Treatment in Pediatric Patients with Osteoporosis Due to Immobilization

Abstract Introduction Osteoporosis is medical condition commonly associated with immobilization in children, which can lead to a vicious cycle of disability, worsening osteoporosis, and recurrent fractures. Currently, bisphosphonates are widely used as a standard therapy in children with osteoporosis, but there are limited data on efficacy according to its dosage and duration. We aimed to evaluate efficacy of bisphosphonate treatment according to the dosage and duration in pediatric patients with osteoporosis due to immobilization.METHOD: We reviewed medical records of pediatric patients who were diagnosed with osteoporosis due to immobilization rated as Gross Motor Function Classification System (GMFCS) grade V, and who received bisphosphonate therapy with regular check-up for at least 1 year. The dosage and duration of the treatment, biochemical laboratory measurements, data of bone densitometry, and the occurrence of side effects were collected. Results Subjects were 21 children. The average duration of bisphosphonate treatment was 2.0 ± 0.9 years, and mean cumulative dose per body weight of bisphosphonate was 7.7 ± 2.5 (mg/kg/year). After the treatment, mean lumbar spine bone mineral contents (BMC) significantly increased from 14.20 ± 8.58 (g) to 19.38 ± 9.89 (g) (p<0.05), lumbar spine bone mineral density (BMD) significantly increased from 0.40 ± 0.14 (g/cm2) to 0.49 ± 0.14 (g/cm2) (p<0.05), and height-adjusted lumbar spine BMD Z-score also showed improvement from -2.66 ± 1.66 to -1.66 ± 1.38 with statistical significance (p<0.05). The cumulative dose and the duration of treatment were not related to its efficacy, but increasing average dose per body weight in each cycle (mg/kg/cycle) showed significant effects on increasing change in height-adjusted lumbar spine BMD z-score (β = 1.065, p <0.05). Discussion BMC, BMD, and height-adjusted BMD z-score significantly increased after bisphosphonate treatment in pediatric patient with osteoporosis due to immobilization. Independent of cumulative dosage and duration, the efficacy of bisphosphonate treatment increased significantly as average dose per body weight in each cycle increased. Further studies with sufficient number of subjects and long term follow-up observation are needed. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Effect of Ionic Calcium and Vitamin D3 in Lumbar Spine Bone Mineral Density of Paediatric Epileptic Patients on Antiepileptic Drugs

Introduction: Epilepsy is one of the most common neurologic conditions occurring in persons under 21 years of age. Vitamin D deficiency is highly prevalent among children with epilepsy. Antiepileptic drugs (AEDs) are associated with decreased Bone Mineral Density (BMD) as AEDs increase catabolism of 25-hydroxy vitamin D by induction of the hepatic P 450 enzyme system, which leads to relative hypocalcaemia, increased levels of parathyroid hormone (PTH) and subsequently low BMD. Aim: To evaluate the association of ionic calcium and vitamin D3 in paediatric epileptic patients who were on AEDs with BMD. Materials and Methods: This was an observational cross-sectional study carried out at Department of Paediatrics, SPMC, Bikaner, Rajasthan, India from December 2020 to November 2021. A total of 150 epileptic patients aged 5 to 15 years who were on AED therapy for more than six months and a comparable group of 130 age and gender matched healthy individuals participated in this study. Serum vitamin D3, Alkaline Phosphatase (ALP), ionic calcium and phosphorous levels were assessed and compared between both the groups. Using OSTEOPRO DEXA BMD at the lumbar spine was calculated. Mann-Whitney test and t-test were used to compare quantitative data whereas Chi-square test was used to compare qualitative data in two groups. Non parametric tests (Spearman Correlation) were used to explore the correlation between the two variables. The p-value of <0.05 was considered to be statistically significant. Results: The mean age of study group and control group were 9.94±2.61 years and 10.09±2.53 years respectively. Mean serum ionic calcium (1.09±0.13 mmol/L) was significantly lower in study group as compared to controls (1.15±0.13 mmol/L) with p-value <0.001. Mean serum phosphorous and serum ALP levels were not significantly different in study and control group. The mean Vitamin D3 level (16.70±5.35 ng/mL) was lower in children receiving AEDs as compared to controls (19.08±5.39 ng/mL) with p-value <0.001. Serum levels of ionic calcium and Vitamin D3 were found to be significantly lower in groups with polytherapy and enzyme inducer group of AEDs (p<0.05) whereas only statistically significant difference in vitamin D3 was found in subjects with more than two years of AED therapy. The mean Lumbar Spine Bone Mineral Apparent Density (LSBMAD) of the study and control group were 0.47±0.14 g/cm² and 0.61±0.12 g/cm² respectively. Conclusion: Epileptic children receiving multiple drugs for longer duration showed more decline in calcium and serum 25 hydroxy vitamin D compared to those with single drug for shorter duration.

Bone densities and bone geometry in children and adolescents with arthrogryposis.

To describe bone densitometry results using lumbar spine dual-energy X-ray absorptiometry and forearm peripheral quantitative computed tomography (pQCT) in children with arthrogryposis multiplex congenita (AMC). Prospective study. Lumbar spine areal bone mineral density (BMD) was measured in 58 participants (mean age 6.8years, range 1month to 19.7years; 26 males). The diagnostic subgroup was Amyoplasia in 27 participants, distal arthrogryposis (unclassified, n=13; type 2A, n=1; type 2B, n=2; type 8, n=2) in 18 patients, an unclassified form of arthrogryposis in 6 patients, and a syndromic form of arthrogryposis in 7 patients. The mean lumbar spine areal BMD was -0.4 (SD: 1.5) which was significantly below 0 (p<0.05, one-sample t-test). The mean lumbar spine bone mineral apparent density z-score (+0.4 [SD: 1.4]), a measure that is largely independent of bone size, was not significantly different from 0 (P>0.05). A subset of 22 patients aged 6years or older (mean age 10.9years, 11 males) had forearm pQCT analysis. Mean z-scores for trabecular and cortical volumetric BMD at the radius were similar to healthy controls. Radius periosteal bone circumference and bone mineral content were appropriate for height. These densitometric results did not differ between patients with Amyoplasia or individuals with other diagnoses. Low areal BMD in children and adolescents with AMC reflects their smaller bone size rather than a specific bone mass deficit. These data do not suggest that children and adolescents with AMC in general require regular monitoring by bone densitometry unless there are specific clinical concerns.

Bisphosphonate therapy for spinal osteoporosis in Hajdu-Cheney syndrome \u2013 new data and literature review

BackgroundHajdu-Cheney syndrome (HCS) (#OMIM 102500) is a rare, autosomal dominant condition that presents in early childhood. It is caused by mutations in the terminal exon of NOTCH2, which encodes the transmembrane NOTCH2 receptor. This pathway is involved in the coupled processes of bone formation and resorption. The skeletal features of HCS include acro-osteolysis of the digits and osteoporosis commonly affecting vertebrae and long bones. Fractures are a prominent feature and are associated with significant morbidity. There is no specific treatment, but with both acro-osteolysis and generalized osteoporosis, it is possible that anti-resorptive treatment might be of benefit. However, to date only a few case reports have evaluated the effectiveness of bisphosphonate treatment.MethodsWe describe the clinical features, treatment regimens and response to bisphosphonate treatment in 7 newly described patients aged 6–39 with HCS, and pooled the data with that from 8 previously published cases (a total of 17 courses of treatment in 15 individuals).ResultsThe mean lumbar spine bone mineral density (BMD) z-score before treatment was − 2.9 (SD 1.2). In 14 courses of treatment (82%), there was an increase in BMD with bisphosphonate treatment, but the impact (in terms of change in spinal BMD z-score) appeared to be less with advancing age (p = 0.01). There was no evidence that acro-osteolysis was prevented.ConclusionsAlthough individual response is variable and age-related, the data support a role for bisphosphonates in preventing or treating spinal osteoporosis in HCS, but bone loss from the lumbar spine may be rapid after cessation.

The safety and effectiveness profile of eldecalcitol in a prospective, post-marketing observational study in Japanese male patients with osteoporosis.

We conducted a post-marketing observational study to investigate the safety and effectiveness of eldecalcitol for the treatment of osteoporosis in a Japanese clinical setting. The observation period was 12months for women and 36months for men. The final results for the female patients have already been published. In this article, the final results for the male patients are reported. A total of 470 male osteoporosis patients were enrolled. The safety analysis set included 431 patients (mean age, 76.8years; mean±SD follow-up period, 631.0±450.3days), and 175 patients continued treatment throughout the 3-year observational period. Adverse drug reactions (ADRs) were reported in 28 patients (6.49%); the most common ADRs were hypercalcemia (1.16%) and renal impairment (1.16%). Serious ADRs were reported in 5 patients (1.16%). Mean serum calcium was within the normal range throughout the observation period. The cumulative incidence of new vertebral and nonvertebral fractures at 36months, estimated by Kaplan-Meier analysis, was 10.23 and 4.06%, respectively. At the last observation, mean lumbar spine bone mineral density was 3.49% higher (P<0.0001) than at baseline, and levels of the bone turnover markers BAP and TRACP-5b were reduced (-14.64%; P=0.0009, and -29.51%; P<0.0001, respectively). In conclusion, the safety and effectiveness of eldecalcitol for the treatment of Japanese male osteoporosis patients was confirmed in clinical practice. Careful monitoring of serum calcium and estimated glomerular filtration rate, both before and during treatment, is necessary to minimize the risk of hypercalcemia and renal impairment while maximizing the effectiveness of eldecalcitol.

Do Textiles Impact DXA Bone Density or Body Composition Results?

External artifacts can confound dual-energy X-ray absorptiometry (DXA) measurements. It is often accepted that garments free of metal do not affect DXA results; however, little data exist in this regard. It is plausible that some textiles absorb radiation and thereby alter DXA results. We hypothesized that some dense or synthetic textiles, for example, reflective materials, might alter DXA-measured bone and soft tissue mass. Hologic and GE Lunar spine phantoms and a Bioclinica prototype total body phantom were imaged on a GE Lunar iDXA and Prodigy densitometer. Each phantom was scanned 10 times to establish mean values. Subsequently, 2 layers of various fabrics were placed over the entire top surface of the phantom, and 10 scans were performed without repositioning. Samples of natural, synthetic, or embellished fabric (including those with reflective material) and of varying thickness were used. Wilcoxon signed rank tests were used to compare the means between bare phantom and textile-covered phantom. Significant differences were demonstrated often, depending on the scanner, phantom, and textile used. A polyester fabric with reflective strip consistently altered measurements. For example, this fabric increased measured mean lumbar spine bone mineral density and total body bone mineral content by 0.008 g/cm2 and 3.6 g, respectively (p < 0.01). Similarly, mean total body fat decreased (−173 g) and lean mass increased (+213 g; p < 0.01). Fat and lean mass were also affected by metallic thread, wool, blend denim, and shiny polyester (p < 0.05), and lean mass was affected by cotton denim and sweatshirt material (p < 0.0003). In conclusion, textiles can affect DXA-measured bone mineral density and body composition results. Even small amounts of reflective material could alter mass measurements by ~25% of the least significant change. Clothing made of dense textiles (e.g., wool and denim) or those with reflective material and metallic thread should be avoided during DXA scanning.

IMPACT OF DEFICIENT NUTRITION IN BONE MASS AFTER BARIATRIC SURGERY.

Background: Essential nutrients are considered for the prevention of the bone loss that occurs after bariatric surgery. Aim: Evaluate nutrients involved in bone metabolism, and relate to serum concentrations of calcium, vitamin D, and parathyroid hormone, and the use of supplements and sun exposure on the bone mass of patients who had undergone gastric bypass surgery. Methods: An observational study, with patients who had undergone the surgery 12 or more months previously, operated group (OG), compared to a control group (CG). Results: Were included 56 in OG and 27 in the CG. The mean age was 36.4±8.5 years. The individuals in the OG, compared to CG, consumed inadequate amounts of protein and daily calcium. The OG had a higher prevalence of low sun exposure, lower levels of 25OH Vitamin D (21.3±10.9 vs. 32.1±11.8 ng/dl), and increased serum levels of parathyroid hormone (68.1±32.9 vs. 39.9±11.9 pg/ml, p<0.001). Secondary hyperparathyroidism was present only in the OG (41.7%). The mean lumbar spine bone mineral density was lower in the OG. Four individuals from the OG had low bone mineral density for chronological age, and no one from the CG. Conclusion: The dietary components that affect bone mass in patients undergoing bariatric surgery were inadequate. The supplementation was insufficient and the sun exposure was low. These changes were accompanied by secondary hyperparathyroidism and a high prevalence of low bone mass in lumbar spine in these subjects.

Bone mass and vitamin D levels in Parkinson's disease: is there any difference between genders?

[Purpose] The aim of this study was to determine the bone mineral density, vitamin D level, and frequencies of osteopenia and osteoporosis in patients with Parkinson’s disease and to compare male and female patients with the controls separately. [Subjects and Methods] One hundred fifteen Parkinson’s disease patients (47 males, 68 females; age range: 55–85 years) and 117 age- and gender-matched controls (47 males, 70 females) were enrolled in the study. Bone mineral density measured by dual-energy X-ray absorptiometry and serum D vitamin levels of each participant were recorded. [Results] The mean lumbar spine, femur neck, and total femur bone mineral density levels, T-scores, and vitamin D levels were found to be significantly lower in Parkinson’s disease patients in both genders. Furthermore, osteoporosis rates were found be significantly higher only in female Parkinson’s disease patients compared with female controls. [Conclusion] Data from the present study revealed that while osteoporosis was significantly higher only in female Parkinson’s disease patients, all Parkinson’s disease patients had lower bone mineral density scores and vitamin D levels compared with the controls regardless of gender, suggesting that clinicians should pay attention to the osteoporosis risk in Parkinson’s disease and that adequate preventive measures should be taken in order to limit the future risk due to osteoporotic fractures.

Abstract P1-09-33: Weight loss and bone health in postmenopausal breast cancer survivors

Abstract Background: The importance of bone health among postmenopausal breast cancer survivors cannot be overemphasized. In addition to bone loss due to aging, secondary bone loss resulting from treatment is a major concern. Although weight loss has adverse effects on bone health in postmenopausal women without cancer, the impact of weight loss on bone health in postmenopausal women with breast cancer is not known. Our objective in this study was to evaluate the effect of weight loss on bone health among overweight/obese postmenopausal breast cancer survivors participating in a weight loss trial. Methods: We conducted this study in a subset of women (postmenopausal, N=81) enrolled in the multi-site Exercise and Nutrition to Enhance Recovery and Good health for You (ENERGY) study. The ENERGY study is a randomized controlled clinical trial designed to achieve a sustained ≥7% loss in body weight among overweight/obese breast cancer survivors with stage I, II or IIIA disease. Weight loss was achieved largely through dietary modification with the addition of physical activity. Bone health was assessed in a subset of women at a single site using bone turnover markers (BTMs) and dual energy X-ray absorptiometry (DXA). Markers of bone formation: osteocalcin, bone-specific alkaline phosphatase (BALP), procollagen type I N-terminal propeptide (PINP) and bone resorption: N-telopeptides of type-I collagen (NTX), C-terminal telopeptide (CTX) were quantified in blood samples collected at baseline, 6 month and 12-month follow-up. DXA T-score was used to measure bone mineral density at baseline and at 12-month follow-up. Generalized estimating equations were used to assess differences in mean values over time as well as from baseline to 6- and 12-month follow-up. Data from intervention and control arm women were used and treated as a cohort. Results: The mean age and body mass index (BMI) of women enrolled in our sub-study were 56 years and 31.6kg/m2, respectively. Majority (54.3%) had stage 2 disease. Mean weight decreased by 5.6 pounds between baseline and 6-month follow-up and 4.3 pounds between baseline and 12-month follow-up. There were statistically significant decreases in mean osteocalcin (2.0ng/ml, p-value&amp;lt;0.001), PINP (7.9ng/ml, p-value&amp;lt;0.001) and NTx (3.65nM BCE/L, p-value&amp;lt;0.001), but not BALP and CTX-1 levels between baseline and 12-month follow-up. No significant changes were observed in mean T-scores, pelvis and lumbar spine bone mineral densities between baseline and 12-month follow-up. Weight change from baseline to 12-month follow-up was weakly inversely associated with changes in DXA T-score (r=-0.25, p-value=0.04) and CTX (r=-0.22, p-value=0.07) but not with other BTMs over the same time period. Conclusion: Weight loss over a 12-month period was associated with decreases in markers of bone formation and resorption but no changes in BMD in overweight/obese postmenopausal women with stage I, II or IIIA breast cancer. Further studies on the association of weight loss and the possible modifying effect of physical activity are needed in order to personalize weight control strategies in overweight/obese breast cancer survivors. Citation Format: Adetunji T Toriola, Jingxia Liu, Patricia A Ganz, Graham A Colditz, Lin Yang, Sonya Izadi, Anna L Schwartz, Kathleen Y Wolin. Weight loss and bone health in postmenopausal breast cancer survivors [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-09-33.

Efficacy and safety of eldecalcitol, a new active vitamin D3 analog, in the bone metabolism of postmenopausal women receiving maintenance hemodialysis.

Eldecalcitol (ELD), a new active vitamin D3 analog developed in Japan, has attracted attention as an effective osteoporotic therapeutic drug. However, because ELD leads to greater calcium absorption than does conventional active vitamin D3, it has yet to be used in patients with renal insufficiency. Therefore, we evaluated the efficacy and safety of ELD treatment in 27 postmenopausal women receiving maintenance dialysis in our institution and underwent ELD treatment (starting at 0.5 μg/day) for 6 months. The mean serum albumin-corrected calcium (Caalb) level was significantly increased following treatment (9.01 ± 0.60 before versus 9.56 ± 0.55 after treatment, mean ± SD). Severe hypercalcemia was prevented through cessation or adjustment of the dosage of calcium-containing phosphate binders or existing active vitamin D. The mean serum phosphorus and intact parathyroid hormone levels were well-controlled throughout. The median levels of bone turnover markers, bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase-5b were significantly decreased. The mean lumbar spine bone mineral density (BMD) was increased, a significant difference being observed in age-matched Z-scores (-0.60 ± 1.6 versus -0.36 ± 1.5, p = 0.018). The average change in lumbar spine BMD after ELD treatment was 3.10%, and in patients with a T-score of <-4.0, it was 5.63%. There was no effect on forearm BMD. Although this study is based on short-term observation in a single institution, our results suggest that ELD could be used to increase bone density in dialysis patients.

A study to evaluate the cause of bone demineralization in gynecological cancer survivors.

An association between treatment for gynecological cancers and risk of osteoporosis has never been formally evaluated. Women treated for these cancers are now living longer than ever before, and prevention of treatment-induced morbidities is important. We aimed to distinguish, in gynecological cancer survivors, whether cancer therapy has additional detrimental effects on bone health above those attributable to hormone withdrawal. We performed a retrospective cross-sectional analysis of dual energy x-ray absorptiometry (DEXA) scan results from 105 women; 64 had undergone bilateral salpingo-oophorectomy (BSO) followed by chemotherapy or radiotherapy for gynecological malignancies, and 41 age-matched women had undergone BSO for benign etiologies. All were premenopausal prior to surgery. The median age at DEXA scan for the cancer group was 42 years, and 66% had received hormonal replacement therapy (HRT) following their cancer treatment. For the benign group, the median age was 40 years, and 87% had received HRT. Thirty-nine percent of cancer survivors had abnormal DEXA scan results compared to 15% of the control group, with the majority demonstrating osteopenia. The mean lumbar spine and femoral neck bone mineral densities (BMDs) were significantly lower in cancer patients. A history of gynecological cancer treatment was associated with significantly lower BMD in a multivariate logistic regression. Women treated for gynecological malignancies with surgery and adjuvant chemotherapy have significantly lower BMDs than age-matched women who have undergone oophorectomy for noncancer indications. Prospective evaluation of BMD in gynecological cancer patients is recommended to facilitate interventions that will reduce the risk of subsequent fragility fractures.

Eliglustat, an Investigational Oral Therapy for Gaucher Disease Type 1: Phase 2 Results After 4 Years of Treatment

AbstractAbstract 1038 Introduction:In Gaucher disease type 1 (GD1), genetically caused deficiency of the enzyme acid β-glucosidase results in undegraded glucosylceramide to accumulate in tissue macrophages (Gaucher cells), resulting in multisystemic manifestations that include thrombocytopenia, anemia, hepatosplenomegaly, and bone disease. A variable clinical course and progression among patients have led to the development of therapeutic goals for the different disease manifestations (Pastores et al., Semin Hematol. 2004;41[suppl 5]:4–14). Eliglustat, a potent and specific inhibitor of glucosylceramide synthase, is under late-stage development as an oral substrate reduction therapy for GD1. Objective:To report long-term efficacy and safety results. Methods:This ongoing, open-label, uncontrolled, multicenter Phase 2 clinical trial enrolled 26 adult patients with GD1 who were not on treatment for the previous 12 months and who had splenomegaly with thrombocytopenia and/or anemia. Patients received 50 mg or 100 mg eliglustat twice daily depending on the plasma trough level. Efficacy outcomes were assessed periodically and included changes from baseline in hemoglobin, platelets, spleen and liver volumes, skeletal manifestations, disease-related biomarker levels, and achievement of therapeutic goals. Results:Nineteen patients completed 4 years of eliglustat treatment; no patient discontinued in the last 2 years. After 4 years of treatment, mean hemoglobin level and platelet count increased by 2.3±1.5 g/dL (from 11.3±1.5 g/dL to 13.6±1.2 g/dL) and 95% (from 68,700±21,200/mm3 to 125,400±51,100/mm3), respectively. Mean spleen and liver volumes (multiples of normal, MN) decreased by 63% (from 17.3±9.5 to 6.1±3.4 MN) and 28% (from 1.7±0.4 MN to 1.2±0.3 MN), respectively. All patients met at least 3 of 4 long-term therapeutic goals (spleen, 100% of patients; liver, 94%; hemoglobin, 100%; platelets, 50%). Baseline platelet count was not found to be a predictive factor of response to treatment. However, a strong linear, statistically significant correlation was found between the mean plasma trough level of eliglustat and the platelet response in patients after 4 years of treatment with eliglustat (r=0.731, P=0.0004). Median chitotriosidase and CCL-18 each decreased by 82%; plasma GL-1 and GM3 normalized. Mean lumbar spine bone mineral density increased by 0.7 Z-score (from −1.2±0.9 to −0.5±1.1) and by 0.8 T-score (from −1.6±1.1 to −0.88±1.3). The greatest increases in lumbar spine T-scores occurred in patients with osteoporosis at baseline. Femur dark marrow, which is believed to reflect Gaucher cell infiltration into bone marrow, was reduced or stable in 17/18 patients. There were no bone crises. Eliglustat was well-tolerated. Most adverse events (AEs) were mild and unrelated to treatment. Ten drug-related AEs, all mild, occurred in 8 patients. No new serious AEs were reported in any patient between 3 and 4 years of treatment. Discussion:Eliglustat continues to show promising efficacy and safety, with clinically meaningful improvements across several disease parameters. Results from two controlled Phase 3 studies in untreated and enzyme replacement therapy maintenance patients will be available in 2013. Disclosures:Peterschmitt:Genzyme: Employment. Lukina:Genzyme: Honoraria, Research Funding. Watman:Genzyme: Membership on an entity's Board of Directors or advisory committees. Pastores:Amicus: Research Funding; Actelion: Research Funding; Biomarin: Research Funding; Genzyme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Shire HGT: Research Funding; Protalix: Research Funding. Arreguin:Genzyme: Research Funding. Rosenbaum:Pfizer: Study Investigator Other. Zimran:Protalix Biotherapeutics: Consultancy; Protalix Biotherapeutics: stock options, stock options Other; Protalix Biotherapeutics: Scientific Advisory Board, Scientific Advisory Board Other; Genzyme: Research Funding; Shire HGT: Honoraria; Actelion: Honoraria; Pfizer: Honoraria. Aguzzi:Genzyme: Employment. Ross:Genzyme: Employment. Puga:Genzyme: Employment.

The Outcome of Surgically Treated Femur Fractures Associated With Long-Term Bisphosphonate Use

Bisphosphonates (BPs) evolved as the mainstay for the treatment of osteoporosis, reducing the incidence of fractures. Recently several publications described the occurrence of low-energy subtrochanteric and femoral shaft fractures associated with long-term BP use. The aim of this study was to describe the outcome of surgically treated femur fractures associated with prolonged BP use. Fifteen patients suffering from 17 atypical femoral fragility fractures associated with long-term (>3 years) BP use were located. Data included fracture type, time of BP use, last bone mineral density DEXA scores for the femoral neck and spine, type of surgery, and the need for revision. Fourteen female patients and one male patient were identified. The median age was 73 years (range, 51-80 years). The mean BP use was 7.8 years (range, 4-13 years). Fourteen patients had low-energy traumatic femoral shaft (proximal and distal) or low subtrochanteric fractures. The mean lumbar spine (for 13 patients) bone mineral density T-score was -3.0, whereas mean femoral neck T-score was -1.8 with only three patients in the osteoporotic range.Fracture healing after the first procedure for patients treated with nails was 54%, with 46% of patients requiring revision surgery. These included nail dynamization, exchange nailing, and one revision to a blade plate. All of these eventually healed. BP-related fractures are a recently described phenomenon. Despite initial osteoporosis, the DEXA scan may appear outside the osteoporotic range for the femoral neck in these patients. In addition, a much higher failure rate with intramedullary nailing requiring revision surgery may occur with these patients.

A phase 2 study of eliglustat tartrate (Genz-112638), an oral substrate reduction therapy for Gaucher disease type 1

AbstractEliglustat tartrate (Genz-112638), a specific inhibitor of glucosylceramide synthase, is under development as an oral substrate reduction therapy for Gaucher disease type 1 (GD1). A multinational, open-label, single-arm phase 2 study of 26 GD1 patients (16 female, 10 male; mean age, 34 years) evaluated the efficacy, safety, and pharmacokinetics of eliglustat tartrate administered twice daily by mouth at 50- or 100-mg doses based on plasma drug concentrations. Entry criteria required splenomegaly with thrombocytopenia and/or anemia. The composite primary efficacy end point required improvement after 52 weeks in at least 2 of these 3 disease manifestations and was met by 77% (95% confidence interval [CI] = 58%-89%) of all patients and 91% (95% CI = 72%-98%) of the 22 patients completing 52 weeks. Statistically significant improvements occurred in mean hemoglobin level (1.62 g/dL; 95% CI =1.05-2.18 g/dL), platelet count (40.3%; 95% CI = 23.7-57.0 g/dL), spleen volume (−38.5%; 95% CI = −43.5%-−33.5%), liver volume (−17.0%; 95% CI = −21.6%-12.3%), and lumbar spine bone mineral density (0.31 Z-score; 95% CI = 0.09-0.53). Elevated biomarkers (chitotriosidase; chemokine CCL18; angiotensin-converting enzyme; tartrate-resistant acid phosphatase) decreased by 35% to 50%. Plasma glucosylceramide and ganglioside GM3 normalized. Eliglustat tartrate was well tolerated: 7 mild, transient adverse events in 6 patients were considered treatment-related. Individual pharmacokinetics varied; mean time to maximal observed concentration was 2.3 hours and mean half-life was 6.8 hours. Eliglustat tartrate appears to be a promising oral treatment for GD1. This study is registered at www.clinicaltrials.gov as #NCT00358150.

Efficacy and safety of bazedoxifene in postmenopausal Asian women

This 6-month study examined the efficacy and safety of bazedoxifene 20 mg in postmenopausal Asian women. Bazedoxifene showed statistically significant improvements over placebo in bone mineral density at all skeletal sites evaluated. Bazedoxifene significantly reduced bone turnover and had favorable effects on lipid parameters. Bazedoxifene was safe and well tolerated. This 6-month, randomized, double-blind, placebo-controlled phase 3 study conducted in China, Korea, and Taiwan evaluated the efficacy and safety of bazedoxifene in postmenopausal Asian women. Generally, healthy postmenopausal Asian women (N=487; mean age, 57.2 years; mean lumbar spine bone mineral density [BMD], -1.1) were randomized to daily therapy with bazedoxifene 20 mg or placebo; all subjects received daily supplemental calcium carbonate 600 mg. The changes from baseline in BMD at the lumbar spine (primary end point) and at other skeletal sites, bone turnover markers, and lipid parameters were evaluated at 6 months. Safety assessments included adverse event (AE) reporting and physical/gynecologic examination. At 6 months, women who received bazedoxifene 20 mg had significantly greater BMD compared with those receiving placebo at the lumbar spine (0.41% vs -0.32%, P<0.01), femoral neck (-0.08% vs -0.69%, P=0.014), trochanter (0.50% vs -0.23%, P=0.010), and total hip (-0.03% vs -0.77%, P<0.001), respectively. Bazedoxifene 20 mg was also associated with significant differences from placebo in median percent reductions from baseline in serum C-telopeptide (-21.8%, P<0.001) and osteocalcin (-12.9%, P<0.001) levels and total (-5.0%, P<0.001) and low-density lipoprotein cholesterol (-9.5%, P<0.001) levels. The incidence of AEs was not different between subjects treated with bazedoxifene and those who received placebo. Bazedoxifene was generally safe and effective in preventing bone loss in this short-term study of postmenopausal Asian women.

Bone Mineral Density and Body Composition in Adolescents with Childhood-Onset Growth Hormone Deficiency

Background/Aims: The aim of the present study was to evaluate bone mineral density (BMD) and body composition of patients with childhood-onset growth hormone (GH) deficiency (GHD) treated with GH during the transition period. Methods: BMD and body composition, measured by dual-energy X-ray absorptiometry, were evaluated at final height and yearly thereafter during 2 years. Twenty-nine of the 40 patients had also been measured before start and during GH therapy. Results: Mean lumbar spine BMD and bone mineral apparent density (BMAD) as well as total body BMD and lean body mass (LBM) SD score (SDS) were significantly lower than normal at final height and during the 2 years thereafter for all patients. Final-height SDS was related to the change in height SDS as well as in LBM SDS during the first year of GH treatment. LBM SDS decreased significantly in the group of patients with GHD without GH treatment (p < 0.01, n = 19). Fat mass SDS increased in all patients. Conclusion: Mean BMD, BMAD and LBM SDS were significantly lower than normal in adolescents with childhood-onset GHD at and 2 years after the attainment of final height.

Efficacy and safety of bazedoxifene in postmenopausal Asian women

This 6-month study examined the efficacy and safety of bazedoxifene 20 mg in postmenopausal Asian women. Bazedoxifene showed statistically significant improvements over placebo in bone mineral density at all skeletal sites evaluated. Bazedoxifene significantly reduced bone turnover and had favorable effects on lipid parameters. Bazedoxifene was safe and well tolerated. This 6-month, randomized, double-blind, placebo-controlled phase 3 study conducted in China, Korea, and Taiwan evaluated the efficacy and safety of bazedoxifene in postmenopausal Asian women. Generally, healthy postmenopausal Asian women (N = 487; mean age, 57.2 years; mean lumbar spine bone mineral density [BMD], −1.1) were randomized to daily therapy with bazedoxifene 20 mg or placebo; all subjects received daily supplemental calcium carbonate 600 mg. The changes from baseline in BMD at the lumbar spine (primary end point) and at other skeletal sites, bone turnover markers, and lipid parameters were evaluated at 6 months. Safety assessments included adverse event (AE) reporting and physical/gynecologic examination. At 6 months, women who received bazedoxifene 20 mg had significantly greater BMD compared with those receiving placebo at the lumbar spine (0.41% vs −0.32%, P < 0.01), femoral neck (−0.08% vs −0.69%, P = 0.014), trochanter (0.50% vs −0.23%, P = 0.010), and total hip (−0.03% vs −0.77%, P < 0.001), respectively. Bazedoxifene 20 mg was also associated with significant differences from placebo in median percent reductions from baseline in serum C-telopeptide (−21.8%, P < 0.001) and osteocalcin (−12.9%, P < 0.001) levels and total (−5.0%, P < 0.001) and low-density lipoprotein cholesterol (−9.5%, P < 0.001) levels. The incidence of AEs was not different between subjects treated with bazedoxifene and those who received placebo. Bazedoxifene was generally safe and effective in preventing bone loss in this short-term study of postmenopausal Asian women.

Final Height Outcome after Three Years of Growth Hormone and Gonadotropin-Releasing Hormone Agonist Treatment in Short Adolescents with Relatively Early Puberty

Our objective was to assess final height (FH) and adverse effects of combined GH and GnRH agonist (GnRHa) treatment in short adolescents born small for gestational age or with normal birth size (idiopathic short stature). Thirty-two adolescents with Tanner stage 2-3, age and bone age (BA) less than 12 yr for girls or less than 13 yr for boys, height sd score (SDS) less than -2.0 SDS or between -1.0 and -2.0 SDS plus a predicted adult height (PAH0) less than -2.0 SDS were randomly allocated to receive GH plus GnRHa (n=17) or no treatment (n=15) for 3 yr. FH was assessed at the age of 18 yr or older in girls or 19 yr or older in boys. FH was not different between treatment and control groups. Treated children had a larger height gain (FH-PAH0) than controls: 4.4 (4.9) and -0.5 (6.4) cm, respectively (P<0.05). FH was higher than PAH0 in 76 and 60% of treated and control subjects, respectively. During follow-up, 50% of the predicted height gain at treatment withdrawal was lost, resulting in a mean gain of 4.9 cm (range, -4.0 to 12.3 cm) compared with controls. Treatment did not affect body mass index or hip bone mineral density. Mean lumbar spine bone mineral density and bone mineral apparent density tended to be lower in treated boys, albeit statistically not significant. Given the expensive and intensive treatment regimen, its modest height gain results, and the possible adverse effect on peak bone mineralization in males, GH plus GnRHa cannot be considered routine treatment for children with idiopathic short stature or persistent short stature after being born small for gestational age.

Growth, Bone Mineral Accretion, and Adrenal Function in Glucocorticoid‐Treated Infants with Hemangiomas – A Retrospective Study

Hemangiomas, common proliferative vascular tumors, can grow rapidly in the first months of life. Although therapy with high-dose oral glucocorticoids is standard for lesions that threaten vital functions or are disfiguring, little is known about the endocrine consequences of this treatment. Using retrospective data, we examined growth velocity, changes in bone mineral density, and adrenal function in infants with hemangiomas treated with systemic glucocorticoids. Treatment consisted of oral prednisolone 2 to 4 mg/kg/day or dexamethasone 1 mg/kg/day. Mean growth velocity Z score on glucocorticoid therapy was -1.41 standard deviations in 13 patients. In four infants with adequate follow-up, growth velocity increased to +1.90 standard deviations after glucocorticoid treatment (Delta growth velocity +3.31 standard deviations). Mean lumbar spine bone mineral density Z score was -2.46 standard deviations before glucocorticoid treatment and -1.08 standard deviations at the end of treatment in six infants. Adrenal function after glucocorticoid therapy was assessed by low-dose adrenocorticotropic hormone stimulation test in 10 infants. Eight had a normal cortisol response, and one had a borderline response. One infant, who had been treated with dexamethasone, had an abnormal test result. In conclusion, systemic glucocorticoid treatment in infants with hemangiomas slowed linear growth, but "catch-up" growth was observed after treatment ceased. Glucocorticoids did not affect bone mineralization adversely. Only 1 of 10 glucocorticoid-treated infants had clear evidence of adrenal insufficiency after therapy was stopped.