scholarly journals Efficacy and Safety of Denosumab Therapy for Osteogenesis Imperfecta Patients with Osteoporosis—Case Series

2018 ◽  
Vol 7 (12) ◽  
pp. 479 ◽  
Author(s):  
Tsukasa Kobayashi ◽  
Yukio Nakamura ◽  
Takako Suzuki ◽  
Tomomi Yamaguchi ◽  
Ryojun Takeda ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Type I Collagen ◽  
Therapeutic Option ◽  
Case Series ◽  
Connective Tissue Disorder ◽  
Tartrate Resistant Acid Phosphatase ◽  
Type I ◽  
Mineral Density ◽  
Bone Specific Alkaline Phosphatase ◽  
Amino Terminal

Osteogenesis imperfecta (OI) is a connective tissue disorder that is characterized by low bone density leading to recurrent fractures. The efficacy of the anti-resorption drug denosumab for OI with osteoporosis is still largely unknown. We herein describe the clinical outcomes of eight osteoporotic cases of OI to examine the effects and safety of denosumab. This retrospective, consecutive case series included eight patients respectively aged 42, 40, 14, 22, 3, 51, 37, and 9 years. We measured the bone mineral density (BMD) of the lumbar 1–4 spine (L-BMD) and bilateral hips (H-BMD), bone-specific alkaline phosphatase, urinary type I collagen amino-terminal telopeptide, and tartrate-resistant acid phosphatase 5b before and during denosumab therapy. Despite multiple pretreatment fractures in the cohort, no fractures or severe side effects, such as hypocalcemia, were observed during the observational period apart from a fracture in a young pediatric girl. Both L-BMD and H-BMD were increased by denosumab in seven of eight cases. Bone turnover markers were inhibited in most cases by denosumab therapy. Denosumab treatment could generally raise BMD without any adverse effects. The agent therefore represents a good therapeutic option for OI with osteoporosis.

scholarly journals Reduced Bone Mineral Density and Increased Bone Metabolism Rate in Young Adult Patients with 21-Hydroxylase Deficiency

2006 ◽  
Vol 91 (11) ◽  
pp. 4453-4458 ◽  
Author(s):  
Mariateresa Sciannamblo ◽  
Gianni Russo ◽  
Debora Cuccato ◽  
Giuseppe Chiumello ◽  
Stefano Mora
Keyword(s):  
Bone Mineral Density ◽  
Alkaline Phosphatase ◽  
Bone Metabolism ◽  
Type I Collagen ◽  
Whole Body ◽  
Type I ◽  
Healthy Controls ◽  
Mineral Density ◽  
Specific Alkaline Phosphatase ◽  
Bone Specific Alkaline Phosphatase

Abstract Context: Patients with congenital adrenal hyperplasia (CAH) receive glucocorticoids as replacement therapy. Glucocorticoid therapy is the most frequent cause of drug-induced osteoporosis. Objective: The objective of the study was to evaluate bone mineral density (BMD) and bone metabolism in CAH patients. Design: This was a cross-sectional observational study. Setting: The study was conducted at a referral center for pediatric endocrinology. Patients and Other Participants: Thirty young patients with the classical form of CAH (aged 16.4–29.7 yr) treated with glucocorticoid from diagnosis (duration of treatment 16.4–29.5 yr) and 138 healthy controls (aged 16.0–30.0 yr) were enrolled. Main Outcome Measures: BMD was measured in the lumbar spine and whole body by dual-energy x-ray absorptiometry. Bone formation and resorption rates were estimated by serum measurements of bone-specific alkaline phosphatase and C-terminal telopeptide of type I collagen, respectively. Results: CAH patients were shorter than controls (women −6.8 and men −13.3 cm). Therefore, several methods were used to account for the effect of this difference on bone measurements. Whole-body BMD measurements were significantly lower, compared with controls (P < 0.03), after controlling for height (on average −2.5% in females and −9.3% in male patients). No differences were found in lumbar spine measurements. Bone-specific alkaline phosphatase and C-terminal telopeptide of type I collagen serum concentrations were higher in CAH patients than control subjects (P < 0.04). BMD measurements and bone metabolism markers did not correlate with the actual glucocorticoid dose or mean dose over the previous 7 yr. Conclusions: Young adult patients with the classical form of CAH have decreased bone density values, compared with healthy controls. This may put them at risk of developing osteoporosis early in life.

scholarly journals Treatment of Glucocorticoid-Induced Osteoporosis with Bisphosphonates Alone, Vitamin D Alone or a Combination Treatment in Eastern Asians: A Meta-Analysis

2019 ◽  
Vol 25 (14) ◽  
pp. 1653-1662
Author(s):  
Junjie Wang ◽  
Hongzhuo Li
Keyword(s):  
Vitamin D ◽  
Femoral Neck ◽  
Combination Treatment ◽  
Type I Collagen ◽  
Meta Analysis ◽  
Type I ◽  
Mineral Density ◽  
Bone Specific Alkaline Phosphatase ◽  
Asian Populations ◽  
Significant Difference

Background: Glucocorticoid (GC)-induced osteoporosis and fractures have become a serious problem for Eastern Asians. Bisphosphonates (BPs), vitamin D and a combination treatment are effective methods to prevent and treat GC-induced osteoporosis. Objective: The study aimed to compare the efficacy of BPs, vitamin D and a combination treatment for preventing and managing GC-induced osteoporosis in Eastern Asians. Methods: A comprehensive search in the PubMed, EMBASE, Web of Science and Cochrane CENTRAL databases was undertaken for randomized controlled trials (RCTs) on the effect of BPs, vitamin D and the combination treatment on GCs-induced osteoporosis in Eastern Asian populations. Primary outcome measures were the change in bone mineral density (BMD) and bone turnover markers. The final search was performed in March 2019. Results: Nine RCTs were included. A total of 545 patients met the inclusion criteria. Compared with vitamin D, BPs and the combination treatment significantly alleviated osteoporosis of the spine and femoral neck in Eastern Asians with GC-induced osteoporosis. At the same time, the change in serum bone-specific alkaline phosphatase (BAP) and serum C-telopeptide of type I collagen (CTX) levels was observed to be significantly less with BPs and the combination treatment with vitamin D alone. No significant difference was found between BPs and the combination treatment in the markers mentioned above. Conclusion: Compared with vitamin D alone, BPs alone and the combination treatment were significantly effective on Eastern Asians with GC-induced osteoporosis. Compared with the combination treatment, BPs alone were observed to be effective enough to increase the BMDs of the spine and femoral neck on both sides and thus prevent GC-induced osteoporosis in Eastern Asians.

scholarly journals EFFECT OF LOVASTATIN NANO DRUG DELIVERY SYSTEM ON BONE MINERAL DENSITY (BMD) AND BIOMECHANICAL PROPERTIES OF TIBIA BONES OF WISTAR RATS

2019 ◽  
pp. 42-48
Author(s):  
RAMANDEEP KAUR ◽  
Makula Ajitha
Keyword(s):  
Wistar Rats ◽  
Type I Collagen ◽  
Biomechanical Properties ◽  
Type I ◽  
Mineral Density ◽  
Bone Specific Alkaline Phosphatase ◽  
Type I Procollagen ◽  
Nanoemulsion Gel ◽  
Male Wistar Rats

Objective: In the present study, transdermal nanoemulsion (NE) gel of lovastatin was investigated for its anti-osteoporosis effect on the long bones of rat i.e. tibia. Methods: Male wistar rats (n=30, weighing 180-200g) were taken for this study and grouped as: 1) control (normal saline daily), 2) Dex (dexamethasone sodium; 25 mg/kg subcutaneously twice a week), 3) Dex+LNG5 (lovastatin nanoemulsion gel; 5 mg/kg/d transdermally daily), 4) Dex+LNG10 (lovastatin nanoemulsion gel; 10 mg/kg/d transdermally daily), and 5) Dex+ALN (alendronate sodium; 0.03 mg/kg/d orally daily). All the treatments were carried out for 60 d. At the end of the experiment, all animals were anesthetized using diethyl ether and collected blood samples from retro-orbital venous plexus of rats in dry eppendorf tubes followed by the sacrifice of animals by cervical dislocation method and collected tibia bones of both the legs for analysis. Results: Bone formation biomarkers (OC: osteocalcin, b-ALP: bone-specific alkaline phosphatase, PINP: N-terminal propeptides of type I procollagen) were significantly improved and resorption biomarkers (CTx: C-terminal cross-linking telopeptides of type-I collagen, TRAcP5b: isoform 5b of tartarate resistant acid phosphatase) were significantly reduced in the LNG5 (p<0.05) and LNG10 (p<0.05) treatment groups when compared to Dex. In vivo anti-osteoporotic results demonstrated the formation of new bone in osteoporotic rat tibias. Biomechanical strength testing demonstrated increased load-bearing capacity of rat tibias in the treated animals in comparison with the osteoporotic group (p<0.05 for LNG5 and p<0.01 for LNG10). Conclusion: Thus, the transdermal NE gel formulation of lovastatin demonstrated the greater potential for the treatment of osteoporosis.

scholarly journals Oxidative Stress and Bone Resorption Interplay as a Possible Trigger for Postmenopausal Osteoporosis

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Carlo Cervellati ◽  
Gloria Bonaccorsi ◽  
Eleonora Cremonini ◽  
Arianna Romani ◽  
Enrica Fila ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lumbar Spine ◽  
Bone Resorption ◽  
Postmenopausal Osteoporosis ◽  
Type I Collagen ◽  
Serum Levels ◽  
Type I ◽  
Bone Homeostasis ◽  
Mineral Density ◽  
Bone Specific Alkaline Phosphatase

The underlying mechanism in postmenopausal osteoporosis (PO) is an imbalance between bone resorption and formation. This study was conducted to investigate whether oxidative stress (OxS) might have a role in this derangement of bone homeostasis. In a sample of 167 postmenopausal women, we found that increased serum levels of a lipid peroxidation marker, hydroperoxides, were negatively and independently associated with decreasedbone mineral density(BMD) in total body (r=-0.192,P<0.05), lumbar spine (r=-0.282,P<0.01), and total hip (r=-0.282,P<0.05), as well as with increased bone resorption rate (r=0.233,P<0.05), as assessed by the serum concentration of C-terminal telopeptide of type I collagen (CTX-1). On the contrary, the OxS marker failed to be correlated with the serum levels of bone-specific alkaline phosphatase (BAP), that is, elective marker of bone formation. Importantly, multiple regression analysis revealed that hydroperoxides is a determinant factor for the statistical association between lumbar spine BMD and CTX-1 levels. Taken together, our data suggest that OxS might mediate, by enhancing bone resorption, the uncoupling of bone turnover that underlies PO development.

scholarly journals The Therapeutic Effectiveness of the Coadministration of Weekly Risedronate and Proton Pump Inhibitor in Osteoporosis Treatment

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Mizue Tanaka ◽  
Soichiro Itoh ◽  
Taro Yoshioka ◽  
Kimihiro Yamashita
Keyword(s):  
Proton Pump Inhibitor ◽  
Proton Pump ◽  
Type I Collagen ◽  
Bodily Pain ◽  
Osteoporosis Treatment ◽  
Physical Parameters ◽  
Type I ◽  
Long Term Effects ◽  
Mineral Density ◽  
Bone Specific Alkaline Phosphatase

This trial was conducted to investigate the long-term effects of proton pump inhibitor (PPI) coadministration on the efficacy of weekly risedronate treatment for osteoporosis. Ninety-six women over 50 years old with low bone mineral density (BMD) participated in this trial. Subjects were randomly divided into 2 groups: a 17.5 mg dose of sodium risedronate was administered weekly, with or without a daily 10 mg dose of sodium rabeprazole (n=49and 47 in the BP + PPI and BP groups, resp.). The following biomarkers were measured at the baseline and every 3 months: bone-specific alkaline phosphatase, N-terminal telopeptide of type I collagen corrected for creatinine, parathyroid hormone, BMD of the lumbar spine, and physical parameters evaluated according to the SF-36v2 Health Survey. Statistical comparisons of these parameters were performed after 6, 12, 18, and 24 months. The Δ values of improvement in physical functioning after 12 months and bodily pain after 6 and 12 months in the BP + PPI group were significantly larger than those in the BP group. These results suggest that PPI does not adversely affect bone metabolism. Alternatively, approved bone formation by concomitant PPI treatment may have had favorable effects on the improvement of bodily pain and physical functions.

scholarly journals Current approach to diagnosis and treatment of children with osteogenesis imperfecta

2019 ◽  
Vol 7 (2) ◽  
pp. 87-102
Author(s):  
Mikhail E. Burtsev ◽  
Aleksandr V. Frolov ◽  
Aleksei N. Logvinov ◽  
Dmitry O. Ilyin ◽  
Andrey V. Korolev
Keyword(s):  
Osteogenesis Imperfecta ◽  
Type I Collagen ◽  
Bone Mineralization ◽  
Bone Dysplasia ◽  
Multidisciplinary Care ◽  
Recovery Process ◽  
Long Bone ◽  
Type I ◽  
Mineral Density ◽  
Genetic Classification

Osteogenesis imperfecta (OI) is a heritable bone dysplasia characterized by bone fragility and long bone deformities. Approximately 85% of OI cases are caused by dominant autosomal mutations in the type I collagen coding genes (COL1A1 and COL1A2), which affect the quantity or structure of collagen. The remaining percentage of cases is caused by mutation in the proteins responsible for posttranslational modification, processing and crosslinking of collagen, bone mineralization, and osteoblast differentiation. In the past decade, new recessive, dominant, and X-linked inheritance. As a result, new types of OI were added to the Sillence classification, and a new genetic classification consisting of XVIII types is formed. Treatment of patients with OI is a complex task which requires a multidisciplinary care. Pharmacological treatment is based on bisphosphonate treatment, which increases the bone mineral density. In this article, we will describe other approaches in which the effectiveness is studied. Surgical treatment of the fractures and deformities of the extremities showed a positive effect on the patients’ quality of life, despite existing complications. There are a lot of debates about the choice between telescopic and non-telescopic fixators. Rehabilitation plays huge role in the recovery process after fracture and surgeries. Osteogenesis imperfecta (OI) is a heritable bone dysplasia characterized by bone fragility and long bone deformities. Approximately 85% of OI cases are caused by dominant autosomal mutations in the type I collagen coding genes (COL1A1 and COL1A2), which affect the quantity or structure of collagen. The remaining percentage of cases is caused by mutation in the proteins responsible for posttranslational modification, processing and crosslinking of collagen, bone mineralization, and osteoblast differentiation. In the past decade, new recessive, dominant, and X-linked inheritance. As a result, new types of OI were added to the Sillence classification, and a new genetic classification consisting of XVIII types is formed. Treatment of patients with OI is a complex task which requires a multidisciplinary care. Pharmacological treatment is based on bisphosphonate treatment, which increases the bone mineral density. In this article, we will describe other approaches in which the effectiveness is studied. Surgical treatment of the fractures and deformities of the extremities showed a positive effect on the patients’ quality of life, despite existing complications. There are a lot of debates about the choice between telescopic and non-telescopic fixators. Rehabilitation plays huge role in the recovery process after fracture and surgeries.

scholarly journals Morphological and mechanical characterization of bone phenotypes in the Amish G610C murine model of osteogenesis imperfecta

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255315
Author(s):  
Rachel Kohler ◽  
Carli A. Tastad ◽  
Amy Creecy ◽  
Joseph M. Wallace
Keyword(s):  
Mouse Model ◽  
Osteogenesis Imperfecta ◽  
Intervention Studies ◽  
Type I Collagen ◽  
Type I ◽  
Micro Computed Tomography ◽  
Mineral Density ◽  
Collagen Formation ◽  
Genotype 2

Osteogenesis imperfecta (OI) is a hereditary bone disease where gene mutations affect Type I collagen formation resulting in osteopenia and increased fracture risk. There are several established mouse models of OI, but some are severe and result in spontaneous fractures or early animal death. The Amish Col1a2G610C/+ (G610C) mouse model is a newer, moderate OI model that is currently being used in a variety of intervention studies, with differing background strains, sexes, ages, and bone endpoints. This study is a comprehensive mechanical and architectural characterization of bone in G610C mice bred on a C57BL/6 inbred strain and will provide a baseline for future treatment studies. Male and female wild-type (WT) and G610C mice were euthanized at 10 and 16 weeks (n = 13–16). Harvested tibiae, femora, and L4 vertebrae were scanned via micro-computed tomography and analyzed for cortical and trabecular architectural properties. Femora and tibiae were then mechanically tested to failure. G610C mice had less bone but more highly mineralized cortical and trabecular tissue than their sex- and age-matched WT counterparts, with cortical cross-sectional area, thickness, and mineral density, and trabecular bone volume, mineral density, spacing, and number all differing significantly as a function of genotype (2 Way ANOVA with main effects of sex and genotype at each age). In addition, mechanical yield force, ultimate force, displacement, strain, and toughness were all significantly lower in G610C vs. WT, highlighting a brittle phenotype. This characterization demonstrates that despite being a moderate OI model, the Amish G610C mouse model maintains a distinctly brittle phenotype and is well-suited for use in future intervention studies.

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