scholarly journals Treatment of osteoporotic fractures in alkaptonuria by teriparatide stimulates bone formation and decreases fracture rate – A report of two cases

Bone Reports ◽  
2021 ◽  
pp. 101151
Author(s):  
L.R. Ranganath ◽  
M. Khedr ◽  
A. Mistry ◽  
S. Vinjamuri ◽  
J.A. Gallagher
Keyword(s):  
Bone Formation ◽  
Osteoporotic Fractures ◽  
Fracture Rate

Romosozumab: A first-in-class sclerostin inhibitor for osteoporosis

2020 ◽  
Vol 77 (23) ◽  
pp. 1949-1956
Author(s):  
Caitlin Prather ◽  
Erin Adams ◽  
Whitney Zentgraf
Keyword(s):  
Clinical Trials ◽  
High Risk ◽  
Bone Resorption ◽  
Bone Formation ◽  
English Language ◽  
Safety Concern ◽  
Osteoporotic Fractures ◽  
Mineral Density ◽  
Treatment Of Osteoporosis ◽  
Poster Presentations

Abstract Purpose The purpose of this article is to review the pharmacology, efficacy, and safety of the sclerostin inhibitor romosozumab for the treatment of osteoporosis, including data from clinical trials of the drug. Summary A review of the literature was performed by searching PubMed and MEDLINE for all relevant articles published between January 2014 and February 2020 using the keywords romosozumab, romosozumab-aqqg, osteoporosis, and fracture. All relevant English-language articles evaluating the pharmacology, efficacy, or safety of romosozumab for the treatment of osteoporosis in humans were included; poster presentations were excluded. Romosozumab has been approved by the Food and Drug Administration and is considered both safe and effective for the treatment of osteoporosis in high-risk postmenopausal females. Phase 2 and phase 3 clinical trials have shown a statistically significant decrease in new vertebral fractures and an increase in bone mineral density with romosozumab use, as compared with both placebo use and use of alternative osteoporosis therapies. The primary safety concern is a potential risk of cardiovascular events; additionally, hypocalcemia must be corrected prior to initiation. Romosozumab is the first anabolic medication that both increases bone formation and decreases bone resorption. Data suggest that romosozumab is more effective than oral bisphosphonates in preventing osteoporotic fractures, though cost and safety concerns must be considered. Conclusion Romosozumab is a novel, 12-month treatment option for postmenopausal women at high risk for osteoporotic fracture that both increases bone formation and decreases bone resorption.

scholarly journals A 6-Year Follow-Up of Fracture Incidence and Volumetric Bone Mineral Density Development in Girls With Turner Syndrome

2017 ◽  
Vol 103 (3) ◽  
pp. 1188-1197 ◽  
Author(s):  
Ondrej Soucek ◽  
Eckhard Schönau ◽  
Jan Lebl ◽  
Johannes Willnecker ◽  
Zdenek Hlavka ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Turner Syndrome ◽  
Bone Strength ◽  
Bone Mineral ◽  
Osteoporotic Fractures ◽  
Volumetric Bone Mineral Density ◽  
Fracture Rate ◽  
Mineral Density ◽  
Bone Parameters ◽  
Normal Bone

Abstract Context Patients with Turner syndrome (TS) are at risk for osteoporotic fractures. Objective The aims of this study were to assess the incidence of clinically important fractures in girls with TS and prospectively describe the development of volumetric bone mineral density (BMD). Design Peripheral quantitative computerized tomography (pQCT) of the radius every other year over the 6 years of observation. Setting Government-funded university referral center. Participants Thirty-two girls with TS, aged 6 to 16 years, were included in the analyses. Fracture incidence was compared with the data in the general population. Bone density and strength were compared with data from 185 healthy girls. Outcomes The main clinical outcome was the fracture occurrence. The secondary outcomes were the changes in Z-scores of the bone parameters. Results Three girls with TS sustained four fractures during 6 years of observation. The fracture rate in TS was not substantially higher than the downward-biased fracture-rate estimate from age-matched, healthy controls (P = 0.48). Whereas the trabecular BMD Z-score decreased with age (β estimate −0.21 ± 0.04, P < 0.001), total bone cross-sectional area correspondingly increased (+0.16 ± 0.04, P < 0.001), which led to normal bone strength. A positive history of incident fractures was not significantly associated with any of the pQCT-derived bone parameters. Conclusions Current pediatric TS patients that are treated with growth hormone and estrogens are not at risk for osteoporotic fractures. Low BMD in TS may be counterweighted by enlarged bone radius, which leads to normal bone strength at the appendicular skeleton.

Adenovirus-mediated expression of vascular endothelial growth factor-a potentiates bone morphogenetic protein9-induced osteogenic differentiation and bone formation

2016 ◽  
Vol 397 (8) ◽  
pp. 765-775 ◽  
Author(s):  
Chang-jun Pi ◽  
Kai-lu Liang ◽  
Zhen-yong Ke ◽  
Fu Chen ◽  
Yun Cheng ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Bone Formation ◽  
Osteogenic Differentiation ◽  
Bone Repair ◽  
Osteoporotic Fractures ◽  
Angiogenic Factor ◽  
Vascular Endothelial ◽  
Akt Inhibitor ◽  
Endothelial Growth Factor

Abstract Mesenchymal stem cells (MSCs) are suitable seed cells for bone tissue engineering because they can self-renew and undergo differentiation into osteogenic, adipogenic, chondrogenic, or myogenic lineages. Vascular endothelial growth factor-a (VEGF-a), an angiogenic factor, is also involved in osteogenesis and bone repair. However, the effects of VEGF-a on osteogenic MSCs differentiation remain unknown. It was previously reported that bone morphogenetic protein9 (BMP9) is one of the most important osteogenic BMPs. Here, we investigated the effects of VEGF-a on BMP9-induced osteogenesis with mouse embryo fibroblasts (MEFs). We found that endogenous VEGF-a expression was undetectable in MSCs. Adenovirus-mediated expression of VEGF-a in MEFs potentiated BMP9-induced early and late osteogenic markers, including alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN). In stem cell implantation assays, VEGF-a augmented BMP9-induced ectopic bone formation. VEGF-a in combination with BMP9 effectively increased the bone volume and osteogenic activity. However, the synergistic effect was efficiently abolished by the phosphoinositide 3-kinase (PI3K)/AKT inhibitor LY294002. These results demonstrated that BMP9 may crosstalk with VEGF-a through the PI3K/AKT signaling pathway to induce osteogenic differentiation in MEFs. Thus, our findings demonstrate the effects of VEGF-a on BMP9-induced bone formation and provide a new potential strategy for treating nonunion fractures, large segmental bony defects, and/or osteoporotic fractures.

High Levels of Periostin in Patients with Multiple Myeloma Correlate with Low Bone Formation, Increased Fracture Rate and Diffuse MRI Pattern

2015 ◽  
Vol 15 ◽  
pp. e223-e224
Author(s):  
E. Terpos ◽  
D. Christoulas ◽  
E. Kastritis ◽  
T. Bagratuni ◽  
V. Koutoulidis ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Formation ◽  
Fracture Rate

scholarly journals Biologicals and bone loss

2012 ◽  
Vol 4 (4) ◽  
pp. 245-247 ◽  
Author(s):  
Charlotte L.M. Krieckaert ◽  
Willem F. Lems
Keyword(s):  
Bone Loss ◽  
Active Rheumatoid Arthritis ◽  
Osteoporotic Fractures ◽  
Fracture Rate ◽  
Healthy Controls ◽  
Mineral Density ◽  
Common Pathway ◽  
Inflammatory Joint Diseases ◽  
Nonvertebral Fractures ◽  
Increased Risk

Inflammatory joint diseases are associated with extra-articular side effects including bone involvement.There is an increased risk of osteoporotic fractures. The pathogeneses of local and generalized bone loss share a common pathway. Early and active rheumatoid arthritis is associated with longitudinal observed bone loss and fracture rate is of vertebral and nonvertebral fractures is doubled compared with matched healthy controls. Lowering disease activity with TNF inhibitors or is associated with stabilisation of bone mineral density by counteracting elevated bone resorption.

scholarly journals Features of bone metabolism in diabetes mellitus

2018 ◽  
Vol 20 (3) ◽  
pp. 82-89 ◽  
Author(s):  
Guzel M. Nurullina ◽  
Guzyal I. Akhmadullina
Keyword(s):  
Diabetes Mellitus ◽  
Bone Formation ◽  
Bone Metabolism ◽  
Bone Remodeling ◽  
Osteoporotic Fractures ◽  
Bone Fragility ◽  
Obesity And Diabetes ◽  
Increased Risk ◽  
Patients With Diabetes ◽  
Low Bone Turnover

Patients with diabetes mellitus (DM) have an increased risk of osteoporotic fractures, which is associated with a bone fragility. Accumulation of advanced glycation end products, hyperhomocysteinemia causes increased apoptosis of osteocytes, decreased bone formation and bone remodeling in DM. Adiponectin stimulates osteocalcin expression and osteoblast differentiation through the activation of AMPK. AMPK-activation stimulates differentiation and mineralization of osteoblasts. Hypoadiponectinemia, which is often observed in obesity and diabetes, can causes bone fragility. Diabetes mellitus is a state of low bone turnover, which is confirmed by decreased markers of bone formation (osteocalcin, P1NP), decreased markers of bone resorption (CTX, TRAP), increased regulatory markers of bone remodeling (OPG, sclerostin). Thus, the study of the pathophysiology of bone metabolism, the level of bone metabolism markers in patients with diabetes mellitus gives broad prospects in understanding the mechanisms of osteoporosis as complication of diabetes mellitus, the selection of targeted therapy and the improvement of early diagnosis of the disease.

scholarly journals Bone Health in Patients with Multiple Sclerosis

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Vit Zikan
Keyword(s):  
Multiple Sclerosis ◽  
Bone Formation ◽  
Bone Structure ◽  
Bone Fractures ◽  
Osteoporotic Fractures ◽  
Mechanical Stimuli ◽  
Osteocyte Apoptosis ◽  
Motor Disability ◽  
Risk Of Falls

Multiple sclerosis (MS) is a gait disorder characterized by acute episodes of neurological defects leading to progressive disability. Patients with MS have multiple risk factors for osteoporotic fractures, such as progressive immobilization, long-term glucocorticoids (GCs) treatment or vitamin D deficiency. The duration of motor disability appears to be a major contributor to the reduction of bone strength. The long term immobilization causes a marked imbalance between bone formation and resorption with depressed bone formation and a marked disruption of mechanosensory network of tightly connected osteocytes due to increase of osteocyte apoptosis. Patients with higher level of disability have also higher risk of falls that combined with a bone loss increases the frequency of bone fractures. There are currently no recommendations how to best prevent and treat osteoporosis in patients with MS. However, devastating effect of immobilization on the skeleton in patients with MS underscores the importance of adequate mechanical stimuli for maintaining the bone structure and its mechanical competence. The physical as well as pharmacological interventions which can counteract the bone remodeling imbalance, particularly osteocyte apoptosis, will be promising for prevention and treatment of osteoporosis in patients with MS.

scholarly journals Fracture Rates in Men With Non-Metastatic Prostate Cancer on Androgen Deprivation Therapy With or Without Anti-Osteoporosis Treatment

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A246-A247
Author(s):  
Hajerah Sonnabend ◽  
Vishnu Priya Pulipati ◽  
Sanford Baim ◽  
Todd Beck ◽  
Ethan M Ritz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Therapy ◽  
Androgen Deprivation Therapy ◽  
Statistical Significance ◽  
Osteoporotic Fractures ◽  
Osteoporosis Treatment ◽  
Androgen Deprivation ◽  
Fracture Rate ◽  
Mineral Density ◽  
Significant Difference

Abstract Introduction: Androgen deprivation therapy (ADT) decreases bone mineral density and increases osteoporotic fracture (OsteoFx) risk. Hypothesis: To assess OsteoFx incidence most predictive of future OsteoFx among men with prostate cancer on ADT. Methods: 4370 electronic medical records were reviewed of adult men with prostate cancer on cancer therapy +/- anti-osteoporotic therapy (Anti-OsteoRx) from 2011–2019. Cancer therapy included ADT (anti-androgens, GnRH agonists & antagonists, orchiectomy) and supplemental cancer therapy (SupplRx) (prostatectomy, brachytherapy, radiation, immunotherapy, and chemotherapy). Anti-OsteoRx included bisphosphonates, denosumab, and parathyroid hormone analogs. Patients with other cancers within 5 years of initial visit, metastasis or traumatic fractures were excluded. Retrospective analysis was done to determine baseline characteristics, type and duration of ADT, Anti-OsteoRx, SupplRx, and OsteoFx incidence. Results: Fracture rate subgroups: • ADT only - Anti-OsteoRx 37/ 374 fractured (9.89%) • ADT only + Anti-OsteoRx 10/52 fractured (19.23%) • ADT + SupplRx + Anti-OsteoRx 2/19 fractured (10.53%) • ADT + SupplRx + Anti-OsteoRx 13/170 fractured (7.65%) Comparing fracture rates between subgroups: • Comparing ADT only +/- Anti-OsteoRx, statistical significance was observed with higher fracture rate in patients taking Anti-OsteoRx (19.23% vs. 9.89%, p < 0.044) • Comparing ADT + SupplRx +/- Anti-OsteoRx, no significant difference in fracture rates due to small number of fractures Comparing combined subgroups: • ADT +/- SupplRx + Anti-OsteoRx 12/71 (16.9%) fractured • ADT +/- SupplRx - Anti-OsteoRx 50/544 (9.19%) fractured • Statistically significant between groups fracture rates was observed (p= 0.042) in patients treated with Anti-OsteoRX. Discussion: Patients receiving Anti-OsteoRx, regardless of their prostate cancer therapies, had higher rates of fractures (16.9 vs. 9.19%, p= 0.042) due to their being selected for therapy based on greater clinical risks. The Anti-OsteoRx group had a higher percentage of glucocorticoid listed as a historical medication (26.8 vs.15.3% vs, p= 0.023), glucocorticoids administered (50.7 vs. 30.3% p=0.001), and anticonvulsants and proton-pump inhibitor use (45.1 vs. 26.5%, p= 0.002). Conclusion: Higher fracture rates were observed in patients on Anti-OsteoRx that could be related to their being selected for treatment based on risk factors known to be associated with osteoporosis. Limited Anti-OsteoRx use in our study is possibly related to lack of standardized guidelines for prevention of osteoporotic fractures in prostate cancer patients. OsteoFx risk assessment utilizing CRF, DXA, and FRAX may prevent fractures in these high-risk patients. Further long-term prospective studies to address these unresolved queries are warranted.

scholarly journals Hormonal Aspects of the Muscle-Bone Unit

2008 ◽  
pp. S159-S169
Author(s):  
I Žofková
Keyword(s):  
Bone Formation ◽  
Muscle Mass ◽  
Mechanical Load ◽  
Osteoporotic Fractures ◽  
Functional System ◽  
Adult Men ◽  
Sexual Steroids ◽  
Common Control ◽  
Igf I ◽  
Functional Complex

Osteoporotic fractures are the result of low density and especially inferior bone quality (microarchitecture) caused by both internal (genes, hormones) and external (life style) influences. Bone mechanosensors are extremely important for the overall integrity of the skeleton, because in response to mechanical load they activate its modeling, resulting in an increase in bone density and strength. The largest physiological loads are caused by muscle contractions. Bone mass in adult men has a closer relationship to muscle mass than is case in women. The sexual differences in the relationship between bone and muscle mass are also apparent in children. Based on the mechanostatic theory, the muscle-bone unit has been defined as a functional system whose components are under the common control of the hormones of the somatotropin-IGF-I axis, sexual steroids, certain adipose tissue hormones and vitamin D. The osteogenic effects of somatotropin-IGF-I system are based on the stimulation of bone formation, as well as increase in muscle mass. Moreover, somatotropin decreases the bone mechanostat threshold and reinforces the effect of physical stress on bone formation. The system, via the muscle-bone unit, plays a significant role in the development of the childhood skeleton as well as in its stability during adulthood. The muscle and bone are also the targets of androgens, which increase bone formation and the growth of muscle mass in men and women, independently of IGF-I. The role of further above-mentioned hormones in regulation of this unified functional complex is also discussed.

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