scholarly journals GH in combination with bisphosphonate treatment in osteogenesis imperfecta

2010 ◽  
Vol 163 (3) ◽  
pp. 479-487 ◽  
Author(s):  
Franco Antoniazzi ◽  
Elena Monti ◽  
Giacomo Venturi ◽  
Roberto Franceschi ◽  
Francesco Doro ◽  
...  
Keyword(s):  
Lumbar Spine ◽  
Osteogenesis Imperfecta ◽  
Growth Velocity ◽  
Bone Age ◽  
Type I ◽  
Mineral Density ◽  
Mass Measurements ◽  
Projected Area ◽  
Bone Mass Measurements ◽  
Risk Rate

ObjectiveTo verify the effects of bisphosphonates (Bps) in combination with recombinant human GH (rGH) in pediatric osteogenesis imperfecta (OI) patients; we focused on possible improvement of bone mineral density (BMD), projected bone areas, growth velocity, and fractures risk.DesignA randomized controlled 1-year clinical trial on 30 prepubertal children (M:F=14:16) affected by OI (type I, IV, and III) being treated with neridronate.MethodsFollowing an observational period of 12 months during ongoing neridronate treatment, the patients were randomly divided into two groups: 15 were treated for 12 months with rGH and neridronate (group Bp+rGH) and 15 continued neridronate alone (group Bp). We evaluated auxological parameters, number of fractures, bone age (BA), bone metabolic parameters, and bone mass measurements (at lumbar spine and radius by dual-energy X-ray absorptiometry).ResultsThe mean variation in percentage of BMD (Δ%BMD) – at lumbar spine (L2–L4), at distal and ultradistal radius – and the projected area of lumbar spine increased significantly in group Bp+rGH (P<0.05). Growth velocity was significantly higher during rGH treatment in group Bp+rGH versus group Bp and versus pretreatment (P<0.05), with no difference in increase in BA or fracture risk rate. Patients with quantitative (-qt) collagen synthesis defects had a higher, although not significant, response to rGH in terms of growth velocity and BMD.ConclusionsIn OI patients, the combined rGH–Bp treatment may give better results than Bp treatment alone, in terms of BMD, lumbar spine projected area and growth velocity, particularly in patients with quantitative defects.

scholarly journals Genetic polymorphisms and their influence on therapeutic response to alendronate-a pilot study

2019 ◽  
Vol 10 (Vol.10, No.3) ◽  
pp. 243-251
Author(s):  
Alina Deniza CIUBEAN ◽  
Laszlo IRSAY ◽  
Rodica Ana UNGUR ◽  
Viorela Mihaela CIORTEA ◽  
Ileana Monica BORDA ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Lumbar Spine ◽  
Bone Turnover ◽  
Postmenopausal Women ◽  
Bone Mineral ◽  
Bone Turnover Markers ◽  
Type I Collagen ◽  
Type I ◽  
Mineral Density ◽  
Turnover Markers

Introduction: Osteoporosis has a strong genetic contribution, and several genes have been shown to influence bone mineral density. Variants in the human genome are considered important causes of differences in drug responses observed in clinical practice. In terms of bone mineral density, about 26–53% of patients do not respond to amino-bisphosphonate therapies, of which alendronate is the most widely used. Material and method: The current study is prospective, observational, analytical, longitudinal and cohort type. It included 25 postmenopausal women treated with alendronate for 1 year. Bone mineral density at lumbar spine and proximal femur was measured and bone turnover markers (C-terminal telopeptide of type I collagen and procollagen 1N-terminal propeptide) were evaluated at 0 and 12 months of treatment. Six single nucleotide polymorphisms in osteoporosis-candidate genes were genotyped (FDPS rs2297480, LRP5 rs3736228, SOST rs1234612, VKORC1 rs9934438, GGPS1 rs10925503 and RANKL rs2277439). Treatment response was evaluated by percentage changes in bone mineral density and bone turnover markers. Results: The heterozygous CT of FDPS rs2297480 showed lower increases in BMD values in the lumbar spine region and the homozygous CC of the GGPS1 rs10925503 showed lower increases in terms of BMD at the total hip region. No association was found for LRP5 rs3736228, SOST rs1234612, VKORC1 rs9934438 and RANKL rs2277439. Conclusions: Romanian postmenopausal women with osteoporosis carrying the CT genotype of FDPS rs2297480 or the CC genotype of GGPS1 rs10925503 could have an unsatisfactory response to alendronate treatment. Key words: osteoporosis; genetic polymorphism; alendronate; bone mineral density; bone turnover markers,

Effects of growth hormone (GH) replacement on bone metabolism and mineral density in adult onset of GH deficiency: results of a double-blind placebo-controlled study with open follow-up

1997 ◽  
Vol 136 (3) ◽  
pp. 282-289 ◽  
Author(s):  
Gerd Finkenstedt ◽  
Rudolf W Gasser ◽  
Günter Höfle ◽  
Christine Watfah ◽  
Leo Fridrich
Keyword(s):  
Lumbar Spine ◽  
Bone Mass ◽  
Bone Turnover ◽  
Gh Deficiency ◽  
Controlled Study ◽  
Type I ◽  
Adult Onset ◽  
Mineral Density ◽  
Markers Of Bone Turnover ◽  
Igf I

Abstract It is known that GH stimulates bone turnover and that GH-deficient adults have a lower bone mass than healthy controls. In order to evaluate the influences of GH replacement therapy on markers of bone turnover and on bone mineral density (BMD) in patients with adult onset GH deficiency, a doubleblind placebo-controlled study of treatment with recombinant human GH (rhGH; mean dose 2·4 IU daily) in 20 patients for 6 months and an extended open study of 6 to 12 months were conducted. Eighteen patients, fourteen men and four women, with a mean age of 44 years with adult onset GH deficiency were evaluated in the study. Compared with placebo, after 6 months serum calcium (2·39±0·02 vs 2·32±0·02 mmol/l, P=0·037) and phosphate (0·97±0·06 vs 0·75±0·05 mmol/l, P=0·011) increased and the index of phosphate excretion (0·03±0·03 vs 0·19±0·02, P<0·001) decreased significantly, and there was a significant increase in the markers of bone formation (osteocalcin, 64·8±11·8 vs 17·4±1·8 ng/ml, P<0·001; procollagen type I carboxyterminal propeptide (PICP), 195·3±26·4 vs 124·0±15·5 ng/ml, P=0·026) as well as those of bone resorption (type I collagen carboxyterminal telopeptide (ICTP), 8·9±1·2 vs 3·3±0·5 ng/ml, P<0·001; urinary hydroxyproline, 0·035±0·006 vs 0·018±0·002 mg/100 ml glomerular filtration rate, P=0·009). BMD did not change during this period of time. IGF-I was significantly higher in treated patients (306·5±45·3 vs 88·7±22·5 ng/ml, P<0·001). An analysis of the data compiled from 18 patients treated with rhGH for 12 months revealed similar significant increases in serum calcium and phosphate, and the markers of bone turnover (osteocalcin, PICP, ICTP, urinary hydroxyproline). Dual energy x-ray absorptiometry (DXA)-measured BMD in the lumbar spine (1·194±0·058 vs 1·133±0·046 g/cm2, P=0·015), femoral neck (1·009±0·051 vs 0·936±0·034 g/cm2, P=0·004), Ward's triangle (0·801±0·055 vs 0·816±0·04 g/cm2, P=0·019) and the trochanteric region (0·869±0·046 vs 0·801±0·033 g/cm2, P=0·005) increased significantly linearly (compared with the individual baseline values). At 12 months, BMD in patients with low bone mass (T-score < −1·0 s.d.) increased more than in those with normal bone mass (lumbar spine 11·5 vs 2·1%, P=0·030, and femoral neck 9·7 vs 4·2%, P=0·055). IGF-I increased significantly in all treated patients. In conclusion, treatment of GH-deficient adults with rhGH increases bone turnover for at least 12 months. BMD in the lumbar spine and the proximal femur increases continuously in this time (open study) and the benefit is greater in patients with low bone mass. Therefore, GH-deficient patients exhibiting osteopenia or osteoporosis should be considered candidates for GH supplementation. However, long-term studies are needed to establish that the positive effects on BMD are persistent and are associated with a reduction in fracture risk. European Journal of Endocrinology 136 282–289

scholarly journals Individualized treatment with denosumab in children with osteogenesis imperfecta – follow up of a trial cohort

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Heike Hoyer-Kuhn ◽  
Mirko Rehberg ◽  
Christian Netzer ◽  
Eckhard Schoenau ◽  
Oliver Semler
Keyword(s):  
Bone Mineral Density ◽  
Lumbar Spine ◽  
Side Effects ◽  
Osteogenesis Imperfecta ◽  
Bone Mineral ◽  
Bone Pain ◽  
Mineral Density ◽  
Osteoclastic Activity ◽  
Activity Marker

Abstract Background Osteogenesis imperfecta (OI) is a rare disease leading to hereditary bone fragility. Nearly 90% of cases are caused by mutations in the collagen genes COL1A1/A2 (classical OI) leading to multiple fractures, scoliosis, short stature and nonskeletal findings as blue sclera, hypermobility of joints, bone pain and delayed motor function development. Bisphosphonates are used in most moderate and severely affected patients assuming that an increase of bone mineral density might reduce fractures and bone pain in patients with OI. Denosumab as a RANK ligand antibody inhibiting osteoclast maturation has been approved for osteoporosis treatment in adults. First data from small clinical trials promised a high efficacy of Denosumab in children with OI. Aim of this analysis was a retrospective evaluation of an individualized biomarker-associated treatment regime with Denosumab in 10 children with classical OI which were followed for 1 year after their participation in a pilot trial with Denosumab. Therefore urinary deoxypyridinoline levels were evaluated frequently as an osteoclastic activity marker and depending on that levels Denosumab injections were scheduled individually. Methods Ten patients (age range: 6.16–12.13 years; all participated in the former OI-AK phase 2 trial (NCT01799798)) were included in the follow-up period. Denosumab was administered subcutaneously depending on the individual urinary excretion course of deoxypyridinoline (DPD/Crea) as osteoclastic activity marker with 1 mg/kg body weight. DPD/Crea levels were evaluated before denosumab administration and afterwards. If patients present after an initial decrease after injection with a re-increase up to the DPD/crea level before Denosumab injection next dosage was planned. Changes of areal bone mineral density (aBMD) using dual energy x-ray absorptiometry of the lumbar spine after 12 month was evaluated. Safety was assessed by bone metabolism markers and side effect reporting. Results During follow-up mean relative change of lumbar aBMD was − 6.4%. Lumbar spine aBMD z-Scores decreased from − 1.01 ± 2.61 (mean ± SD) to − 1.91 ± 2.12 (p = 0.015). Mobility changed not significantly (GMFM-88 -6.49 ± 8.85% (p = 0.08). No severe side effects occurred. Dose intervals could be extended in the mean from 12 weeks previously to 20.3 weeks. Conclusions On average, it was possible to prolong the intervals between drug administrations and to reduce the total dose about by 25% without a decrease of mobility or change of vertebral shape despite a reduction of lumbar aBMD during 1 year of biomarker-directed Denosumab treatment. Further trials are necessary to balance side effects and highest efficacy in children.

scholarly journals Serum 24,25-Dihydroxyvitamin D Concentrations in Osteogenesis Imperfecta: Relationship to Bone Parameters

2012 ◽  
Vol 97 (4) ◽  
pp. 1243-1249 ◽  
Author(s):  
Thomas Edouard ◽  
Abdallah Husseini ◽  
Francis H. Glorieux ◽  
Frank Rauch
Keyword(s):  
Osteogenesis Imperfecta ◽  
Serum Levels ◽  
Collagen Type I ◽  
Type I ◽  
Mineral Density ◽  
Serum 25Ohd ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
And Gender ◽  
Serum Pth

Background: Several studies suggest that 24,25-dihydroxyvitamin D [24,25(OH)2D] may have an effect on bone mass and metabolism. Objective: We evaluated the relationship between serum 24,25(OH)2D levels and bone density and bone metabolism in children with a primary bone disorder—osteogenesis imperfecta (OI). Materials and Methods: The study included 132 patients (age, 1.1 to 17.9 yr; 67 girls) with OI types I, III, or IV who had not received bisphosphonate treatment at the time of analysis. Results: Serum 24,25(OH)2D levels were significantly higher in OI type III than in OI type I or IV. Serum 24,25(OH)2D concentrations were positively correlated with serum 25-hydroxyvitamin D (25OHD) levels and negatively correlated with serum PTH levels, and were not correlated with serum 1α,25-dihydroxyvitamin D [1,25(OH)2D]. The ratio between serum 24,25(OH)2D and 25OHD was negatively correlated with age and was independent of serum 25OHD concentrations. Regression analysis revealed that OI severity (P = 0.04), serum 25OHD levels (P &lt; 0.001), and serum PTH concentrations (P = 0.045), but not age, gender, or serum 1,25(OH)2D, were independent predictors of serum 24,25(OH)2D levels. No correlation was found between serum 24,25(OH)2D levels or the ratio between serum 24,25(OH)2D and 25OHD and lumbar spine bone mineral density z-scores or bone marker levels (serum osteocalcin and urinary collagen type I N-telopeptide) after adjusting for OI type, age, and gender. Conclusion: Patients with more severe OI type had higher 24,25(OH)2D serum levels and higher serum 24,25(OH)2D to 25OHD ratios, suggesting an increased 25OHD-24-hydroxylase activity.

Alpha-Ketoglutarate Decreases Serum Levels of C-terminal Cross-Linking Telopeptide of Type I Collagen (CTX) in Postmenopausal Women with Osteopenia: Six-Month Study

2007 ◽  
Vol 77 (2) ◽  
pp. 89-97 ◽  
Author(s):  
Filip ◽  
Pierzynowski ◽  
Lindegard ◽  
Wernerman ◽  
Haratym-Maj ◽  
...  
Keyword(s):  
Lumbar Spine ◽  
Postmenopausal Women ◽  
Type I Collagen ◽  
Skeletal Development ◽  
Serum Levels ◽  
Study Groups ◽  
Type I ◽  
Mineral Density ◽  
Double Blind ◽  
Beneficial Effects

Several studies have shown that α-ketoglutaric acid (AKG) increases serum levels of proline and has beneficial effects on skeletal development. We studied the effect of α-ketoglutaric (AKG) acid calcium salt (6 g AKG and 1.68 Ca/day) or calcium alone (1.68 Ca/day) on serum C-terminal cross-linked telopeptide of type I collagen (CTX) and osteocalcin (OC), as well as on lumbar spine bone mineral density (BMD) in a randomized, parallel group, double-blind, 6-month study conducted on 76 postmenopausal women with osteopenia. The maximum decrease of the mean CTX level in the AKG-Ca group was observed after 24 weeks (37.0%, p = 0.006). The differences in CTX between study groups were statistically significant after 12 and 24 weeks. The OC serum level was not affected by treatments. The BMD of the AKG-Ca group increased by 1.6% from baseline; however, the difference between treatment groups was estimated as 0.9% (non-significant). This study suggests the potential usefulness of AKG-Ca in osteopenic postmenopausal women. AKG-Ca induced beneficial changes in serum CTX, which was consistent with preserving the bone mass in the lumbar spine; however, the long-term effect needs to be further investigated.

scholarly journals A novel missense mutation in P4HB causes mild osteogenesis imperfecta

2019 ◽  
Vol 39 (4) ◽  
Author(s):  
Lujiao Li ◽  
Dichen Zhao ◽  
Wenbin Zheng ◽  
Ou Wang ◽  
Yan Jiang ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Missense Mutation ◽  
Bone Fractures ◽  
Novel Mutation ◽  
Pathogenic Mutation ◽  
Chinese Family ◽  
Type I ◽  
Mineral Density ◽  
Type I Procollagen ◽  
Helix Formation

AbstractOsteogenesis imperfecta (OI) is a rare heritable bone disorder characterized by low bone mineral density (BMD), recurrent bone fractures, and progressive bone deformities. P4HB encodes protein disulfide isomerase (PDI) and is identified as a novel candidate gene of OI. The purposes of the present study are to detect pathogenic mutation, to evaluate the phenotypes of a Chinese family with mild OI, and to investigate the effects of bisphosphonates on bone of the proband. We detected the pathogenic mutation by next generation sequencing and Sanger sequencing. Laboratory and radiological investigations were conducted to evaluate the phenotypes. The proband was a 12-year-old girl with low BMD, history of recurrent non-traumatic fractures, slight scoliosis, with bluish grey sclera and ligamentous laxity. Her father suffered from one fragility fracture and slight wedge changes of vertebras, with bluish grey sclera. We identified a novel heterozygous missense mutation (c.692A>C, p.His231Pro) in P4HB in the proband and her father. This mutation was predicted to affect the combination of PDI with type I procollagen and lead to the disorder of its triple helix formation. Bisphosphonates were effective in reducing bone resorption and increasing BMD of the proband with well tolerance. In conclusion, we identified a novel mutation in P4HB in a Chinese family with mild OI, which expanded the genotypic and phenotypic spectrum of OI. Bisphosphonates were effective to this extremely rare OI induced by P4HB mutation.

scholarly journals 319. SWORD 1 and 2: Switch from TDF Containing Regimen to DTG+RPV Maintains Bone Mineral Density and Decreases Bone Turnover Markers Over 148 Weeks

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S169-S170
Author(s):  
Lesley Kahl ◽  
Grace A McComsey ◽  
Monica Coronado Poggio ◽  
Sergio Lupo ◽  
Joss de Wet ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Lumbar Spine ◽  
Bone Turnover ◽  
Bone Mineral ◽  
Bone Turnover Markers ◽  
Type I ◽  
Mineral Density ◽  
Total Hip ◽  
Turnover Markers ◽  
Switch Group

Abstract Background HIV infection and antiretroviral therapy (ART), particularly tenofovir (TDF), is associated with loss of bone mineral density (BMD). The SWORD studies demonstrated noninferiority of the 2-drug regimen (2DR) dolutegravir (DTG) + rilpivirine (RPV) to continuing current triple-therapy ART (CAR) at 48 weeks and continued viral suppression on DTG+RPV through Week 148. A substudy of SWORD 1 and 2 evaluated a change in BMD by DEXA for those participants who switched from triple ART containing TDF to DTG+RPV. The primary analysis reported at 48 weeks showed a significant increase in total hip and lumbar spine BMD and a significant decrease in bone turnover markers in patients receiving DTG+RPV compared with CAR. Here we present data through Week 148. Methods HIV-infected adult patients with HIV-1 RNA < 50 c/mL received ART containing TDF for ≥6 months prior to randomization to DTG+RPV (Early Switch group, ES) or CAR on Day 1 (Baseline, BL) through Week 48 in SWORD-1/2. CAR patients suppressed at Week 48 switched to DTG+RPV at Week 52 (Late Switch group, LS). Hip and lumbar spine BMD were measured by DEXA scans read centrally. Secondary endpoints include a change in BMD and bone turnover markers through Week 148. Results Following switch to DTG+RPV significant increases were observed for total hip in the ES and LS groups through 100 weeks with a non-significant increase at Week 148 in ES (Figure 1a). Lumbar spine BMD significantly increased from BL at 48 weeks post switch, remained increased, though not significantly from BL through Week 148 (Figure 1b). The BMD of the LS group was similar to that of the ES group through 100 weeks exposure. The majority of patients remained in their pre-switch T-score category or improved a category for both hip and spine through Wk148 (Table 1). Through Wk148, BMI increased minimally and bone turnover markers significantly decreased (P < 0.001 to 0.042 across markers) from BL/LS BL except Type I Collagen C-Telopeptide at Wk148 in the LS group (P = 0.279). Conclusion Switch to the DTG+RPV 2DR was associated with sustained improvements in BMD through Week 148, along with a reduction in bone markers. The favorable effects on skeletal health were observed despite the ageing of study patients and other factors decreasing BMD. A switch to DTG+RPV in suppressed patients provides a robust option for preserving bone health while continuing suppressive HIV treatment. Disclosures All authors: No reported disclosures.

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 Bone Mineral Density in Children and Adolescents with Congenital Adrenal Hyperplasia

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Paulo Alonso Garcia Alves Junior ◽  
Daniel Luis Gilban Schueftan ◽  
Laura Maria Carvalho de Mendonça ◽  
Maria Lucia Fleiuss Farias ◽  
Izabel Calland Ricarte Beserra
Keyword(s):  
Bone Mineral Density ◽  
Lumbar Spine ◽  
Congenital Adrenal Hyperplasia ◽  
Bone Mineral ◽  
Bone Age ◽  
Adrenal Hyperplasia ◽  
Mineral Density ◽  
Classic Congenital Adrenal Hyperplasia ◽  
Paediatric Patients ◽  
Total Body

Chronic glucocorticoid therapy is associated with reduced bone mineral density. In paediatric patients with congenital adrenal hyperplasia, increased levels of androgens could not only counteract this effect, but could also advance bone age, with interference in the evaluation of densitometry. We evaluate bone mineral density in paediatric patients with classic congenital adrenal hyperplasia taking into account chronological and bone ages at the time of the measurement. Patients aged between 5 and 19 years underwent radiography of the hand and wrist followed by total body and lumbar spine densitometry. Chronological and bone ages were used in the scans interpretation. In fourteen patients, mean bone mineral densityZ-score of total body to bone age was −0.76 and of lumbar spine to bone age was −0.26, lower than those related to chronological age (+0.03 and +0.62, resp.). MeanZ-score differences were statistically significant (P=0.004for total body andP=0.003for lumbar spine). One patient was classified as having low bone mineral density only when assessed by bone age. We conclude that there was a reduction in the bone mineral densityZ-score in classic congenital adrenal hyperplasia paediatric patients when bone age was taken into account instead of chronological age.

Sign in / Sign up

Export Citation Format

Share Document