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The overarching goal of osteoporosis management is to prevent fractures. A goal-directed approach to long-term management of fracture risk helps ensure that the most appropriate initial treatment and treatment sequence is selected for individual patients. Goal-directed treatment decisions require assessment of clinical fracture history, vertebral fracture identification (using vertebral imaging as appropriate), measurement of bone mineral density (BMD) and consideration of other major clinical risk factors. Treatment targets should be tailored to each patient's individual risk profile and based on the specific indication for beginning treatment, including recency, site, number and severity of prior fractures, and BMD levels at the total hip, femoral neck, and lumbar spine. Instead of first-line bisphosphonate treatment for all patients, selection of initial treatment should focus on reducing fracture risk rapidly for patients at very high and imminent risk, such as in those with recent fractures. Initial treatment selection should also consider the probability that a BMD treatment target can be attained within a reasonable period of time and the differential magnitude of fracture risk reduction and BMD impact with osteoanabolic versus antiresorptive therapy. This position statement of the ASBMR/BHOF Task Force on Goal-Directed Osteoporosis Treatment provides an overall summary of the major clinical recommendations about treatment targets and strategies to achieve those targets based on the best evidence available, derived primarily from studies in older postmenopausal women of European ancestry.
Goal-directed treatment can help healthcare providers recommend the best treatments for individual patients to prevent fractures. The goal-directed strategy considers the site, number and recency of prior fractures. This may require imaging for spine fractures, which may not have caused pain. Treatment decisions also require bone mineral density (BMD) measurement and consideration of other major risk factors. In contrast to the standard approach, same first treatment for all, treatment selection is tailored to an individual's risk. In patients with recent fractures of the spine, hip or pelvis, fracture risk is very high and treatment should rapidly reduce that risk. For others, the target is a specific BMD level and should consider the likelihood that the treatment target can be attained within a reasonable period of time, which differs for osteoporosis medications. After initial therapy, BMD should be assessed to determine if the target has been achieved. If so, strategies should focus on maintaining BMD. If the target is not yet achieved, treatment should be intensified, or continued if it is already the most potent option. This position statement represents a consensus of expert recommendations about treatment targets and strategies to achieve those targets based on the best available evidence.
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PURPOSE: The purpose of this observational study was to investigate the effectiveness and safety of romosozumab (ROMO) and teriparatide (TPTD) in a clinical setting. METHODS: 315 postmenopausal women were included based on the reimbursement criteria for ROMO and TPTD at the Department of Endocrinology at Aarhus University Hospital. ROMO: Bone Mineral Density (BMD) T-score <-2.5 (femoral neck (FN), total hip (TH), or lumbar spine (LS)) + a fragility fracture (hip, spine, pelvis, distal forearm, or proximal humerus) within 3 years. TPTD: Within 3 years ≥2 vertebral fractures or 1 vertebral fracture + BMD T-score (FN, TH, or LS) <-3. Data was collected from medical records. The primary end point was percentage change from baseline in BMD (FN, TH, and LS) at month 12. BMD was measured by DXA. RESULTS: At month 12 ROMO led to significantly (p<0.001) larger increases than TPTD in BMD (FN: 4.8% vs. 0.2%, TH: 5.7% vs. 0.3%, and LS: 13.7% vs. 9.3%). Discontinuation rate was lower with ROMO than with TPTD. Lower incidence of cardiovascular adverse events was observed with ROMO compared to TPTD. Treatment-naïve patients had non-significantly higher BMD increases compared to previously treated patients with both ROMO and TPTD. CONCLUSION: Treatment with romosozumab yields larger increases in bone mineral density than teriparatide after 12 months and a higher rate of completion.
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Osteogenesis imperfecta (OI) is a rare genetic disorder commonly caused by variants of the type I collagen genes COL1A1 and COL1A2. OI is associated with increased bone fragility, bone deformities, bone pain, and reduced growth. Setrusumab, a neutralizing antibody to sclerostin, increased areal bone mineral density (aBMD) in a 21-week phase 2a dose escalation study. The phase 2b Asteroid (NCT03118570) study evaluated the efficacy and safety of setrusumab in adults. Adults with a clinical diagnosis of OI type I, III, or IV, a pathogenic variant in COL1A1/A2, and a recent fragility fracture were randomized 1:1:1:1 to receive 2, 8, or 20 mg/kg setrusumab doses or placebo by monthly intravenous infusion during a 12-month treatment period. Participants initially randomized to the placebo group were subsequently reassigned to receive setrusumab 20 mg/kg open label. Therefore, only results from the 2, 8, and 20 mg/kg double-blind groups are presented herein. The primary endpoint of Asteroid was change in distal radial trabecular vBMD from baseline at Month 12, supported by changes in high-resolution peripheral quantitative computed tomography micro finite element-derived bone strength. A total of 110 adults were enrolled with similar baseline characteristics across treatment groups. At 12 months, there was a significant increase in mean (SE) failure load in the 20 mg/kg group (3.17% [1.26%]) and stiffness in the 8 (3.06% [1.70%]) and 20 mg/kg (3.19% [1.29%]) groups from baseline. There were no changes in radial trabecula vBMD (p > 0.05). Gains in failure load and stiffness were similar across OI types. There were no significant differences in annualized fracture rates between doses. Two adults in the 20 mg/kg group experienced related serious adverse reactions. Asteroid demonstrated a beneficial effect of setrusumab on estimates of bone strength across the different types of OI and provides the basis for additional phase 3 evaluation.
Osteogenesis imperfecta, or OI, is a rare disorder affecting patients' bones causing pain and an increased chance of the bone breaking. Setrusumab is a possible treatment for OI being studied in a clinical trial called Asteroid. The goal of Asteroid was to determine which dose of setrusumab helped adults with OI the most: 2, 8, or 20 mg/kg. Researchers looked at the density of patients' bones and estimated how strong their bones were before setrusumab and again after 12 months of treatment to see how they improved with treatment. Researchers could compare these improvements to see which dose of setrusumab helped patients the most. Patients on the highest dose of setrusumab (20 mg/kg) experienced improvements in the density of their arm bones (radius) and leg bones (tibia) after 12 months. The strength of these bones also improved. The density of other bones including the spine, hip, and the overall skeleton (total body) also improved with treatment. Of patients who had side effects after receiving setrusumab, most were mild or moderate intensity. Overall, setrusumab improved the bones of patients with OI with no serious safety concerns. More studies will include even more patients to see how setrusumab can improve their bones.
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BACKGROUND & AIM: Patients with an ileostomy are at increased risk of dehydration and sodium depletion. Treatments recommended may include oral rehydration solutions (ORS). We aimed to investigate if protein type or protein hydrolysation affects absorption from iso-osmolar ORS in patients with an ileostomy. METHODS: This was a randomised, double-blinded, active comparator-controlled 3 × 3 crossover intervention study. We developed three protein-based ORS with whey protein isolate, caseinate or whey protein hydrolysate. The solutions contained 40-48 g protein/L, 34-45 mmol sodium/L and had an osmolality of 248-270 mOsm/kg. The patients ingested 500 mL/d. The study consisted of three 4-week periods with a >2-week washout between each intervention. The primary outcome was wet-weight ileostomy output. Ileostomy output and urine were collected for a 24-h period before and after each intervention. Additionally, blood sampling, dietary records, muscle-strength tests, bioimpedance analyses, questionnaires and psychometric tests were conducted. RESULTS: We included 14 patients, of whom 13 completed at least one intervention. Ten patients completed all three interventions. Wet-weight ileostomy output did not change following either of the three interventions and did not differ between interventions (p = 0.38). A cluster of statistically significant improvements related to absorption was observed following the intake of whey protein isolate ORS, including decreased faecal losses of energy (-365 kJ/d, 95% confidence interval (CI), -643 to -87, p = 0.012), potassium (-7.8 mmol/L, 95%CI, -12.0 to -3.6, p = 0.001), magnesium (-4.0 mmol/L, 95%CI, -7.4 to -0.7, p = 0.020), improved plasma aldosterone (-4674 pmol/L 95%CI, -8536 to -812, p = 0.019), estimated glomerular filtration rate (eGFR) (2.8 mL/min/1.73 m2, 95%CI, 0.3 to 5.4, p = 0.03) and CO2 (1.7 mmol/L 95%CI, 0.1 to 3.3, p = 0.04). CONCLUSION: Ingestion of 500 mL/d of iso-osmolar solutions containing either whey protein isolate, caseinate or whey protein hydrolysate for four weeks resulted in unchanged and comparable ileostomy outputs in patients with an ileostomy. Following whey protein isolate ORS, we observed discrete improvements in a series of absorption proxies in both faeces and blood, indicating increased absorption. The protein-based ORS were safe and well-tolerated. Treatments should be tailored to each patient, and future studies are warranted to explore treatment-effect heterogeneity and whether different compositions or doses of ORS can improve absorption and nutritional status in patients with an ileostomy. GOV STUDY IDENTIFIER: NCT04141826.
Subject(s)
Cross-Over Studies , Fluid Therapy , Ileostomy , Rehydration Solutions , Whey Proteins , Humans , Double-Blind Method , Male , Female , Whey Proteins/administration & dosage , Middle Aged , Aged , Rehydration Solutions/administration & dosage , Fluid Therapy/methods , Dehydration/therapy , Caseins/administration & dosage , Protein Hydrolysates/administration & dosage , AdultABSTRACT
Osteogenesis imperfecta (OI) is a Mendelian connective tissue disorder associated with increased bone fragility and other clinical manifestations most commonly due to abnormalities in production, structure, or post-translational modification of type I collagen. Until recently, most research in OI has focused on the pediatric population and much less attention has been directed at the effects of OI in the adult population. This is a narrative review of the literature focusing on the skeletal as well as non-skeletal manifestations in adults with OI that may affect the aging individual. We found evidence to suggest that OI is a systemic disease which involves not only the skeleton, but also the cardiopulmonary and gastrointestinal system, soft tissues, tendons, muscle, and joints, hearing, eyesight, dental health, and women's health in OI and potentially adds negative affect to health-related quality of life. We aim to guide clinicians as well as draw attention to obvious knowledge gaps and the need for further research in adult OI.
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OBJECTIVES: To investigate the diagnostic accuracy of high-resolution peripheral quantitative computed tomography (HR-pQCT) to assess erosive progression during one year compared to conventional radiography (CR) in rheumatoid arthritis (RA). METHODS: This prospective study included 359 patients with RA (disease duration ≥ 5 years) between March 2018 and October 2020. HR-pQCT and CR were obtained at inclusion and after one year. Erosive assessment was performed at two metacarpophalangeal joints of the dominant hand using HR-pQCT and progression was defined as an increase in erosion number ≥ 1 or an increase in erosive volume > least significant change. CR of hands, wrists, and feet were evaluated using Sharp/van der Heijde scores and erosive progression was defined as a 1.1-point increase in erosion score according to the smallest detectable change. RESULTS: In paired analyses (n = 310), erosive progression was identified in 30 patients using CR and in 40 patients using HR-pQCT. In the 40 patients with erosive progression on HR-pQCT, progression was not identified by CR in 33 patients. Adding HR-pQCT to CR doubled the proportion of patients identified with progression from 30 (10%) to 63 (20%) patients. Using CR as the reference, the sensitivity (% (95% CI)) of HR-pQCT for identifying erosive progression was 23.3 (9.9-42.3) and the specificity was 88.2 (83.8-91.7). CONCLUSION: A substantial proportion of patients with erosive progression are overlooked using CR only to monitor erosive progression. Adding high-resolution peripheral CT to CR doubles the proportion of patients, who may benefit from individualised therapy targeting erosive progression in RA.
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BACKGROUND: Osteoporosis patient education is offered in many countries worldwide. When evaluating complex interventions like these, it is important to understand how and why the intervention leads to effects. This study aimed to develop a program theory of osteoporosis patient education in Danish municipalities with a focus on examining the mechanisms of change i.e. what is about the programs that generate change. METHODS: The program theory was developed in an iterative process. The initial draft was based on a previous published systematic review, and subsequently the draft was continually refined based on findings from observations (10 h during osteoporosis patient education) and interviews (individual interviews with six employees in municipalities and three health professionals at hospitals, as well as four focus group interviews with participants in patient education (in total 27 informants)). The transcribed interviews were analyzed using thematic analysis and with inspiration from realist evaluation the mechanisms as well as the contextual factors and outcomes were examined. RESULTS: Based on this qualitative study we developed a program theory of osteoporosis patient education and identified four mechanisms: motivation, recognizability, reassurance, and peer reflection. For each mechanism we examined how contextual factors activated the mechanism as well as which outcomes were achieved. For instance, the participants' motivation is activated when they meet in groups, and thereafter outcomes such as more physical activity may be achieved. Recognizability is activated by the participants' course of disease, which may lead to better ergonomic habits. Reassurance may result in more physical activity, and this mechanism is activated in newly diagnosed participants without previous fractures. Peer reflection is activated when the participants meet in groups, and the outcome healthier diet may be achieved. CONCLUSIONS: We developed a program theory and examined how and why osteoporosis patient education is likely to be effective. Understanding these prerequisites is important for future implementation and evaluation of osteoporosis patient education.
Subject(s)
Osteoporosis , Patient Education as Topic , Qualitative Research , Humans , Denmark/epidemiology , Osteoporosis/therapy , Patient Education as Topic/methods , Female , Male , Program Evaluation/methods , Program Development/methods , Middle Aged , AgedABSTRACT
Musculoskeletal research should synergistically investigate bone and muscle to inform approaches for maintaining mobility and to avoid bone fractures. The relationship between sarcopenia and osteoporosis, integrated in the term 'osteosarcopenia', is underscored by the close association shown between these two conditions in many studies, whereby one entity emerges as a predictor of the other. In a recent workshop of Working Group (WG) 2 of the EU Cooperation in Science and Technology (COST) Action 'Genomics of MusculoSkeletal traits Translational Network' (GEMSTONE) consortium (CA18139), muscle characterization was highlighted as being important, but currently under-recognized in the musculoskeletal field. Here, we summarize the opinions of the Consortium and research questions around translational and clinical musculoskeletal research, discussing muscle phenotyping in human experimental research and in two animal models: zebrafish and mouse.
Subject(s)
Phenotype , Animals , Humans , Muscle, Skeletal/metabolism , Zebrafish , Mice , Sarcopenia/metabolism , Sarcopenia/physiopathology , Musculoskeletal Diseases/physiopathology , Musculoskeletal Diseases/genetics , Osteoporosis/metabolism , Osteoporosis/pathologyABSTRACT
BACKGROUND: Osteoporosis is a chronic progressive disease that requires lifelong monitoring and treatment. Sequencing from one treatment to another at different ages and stages of disease is an approach that can maximize benefits and avoid potential risks from long-term treatment with a single agent. OBJECTIVE: This article reviews clinical trial data in postmenopausal women that evaluate the effects of antiresorptive agents followed by other antiresorptives, osteoanabolic agents followed by antiresorptives, and antiresorptives followed by osteoanabolic medications. METHODS: Literature review and discussion. RESULTS: When medications are discontinued, in the absence of sequential therapy, bone turnover rates return to baseline or above baseline, and bone loss occurs. The rate of bone loss differs for different treatments, with a very slow decline after stopping bisphosphonates and a particularly rapid decline after stopping denosumab. Careful attention to osteoporosis medication transitions can mitigate bone density loss and its consequences. For women who remain at high risk, switching from bisphosphonates to the more potent antiresorptive, denosumab, will result in further improvement in bone mineral density (BMD). When indicated, stopping denosumab can be accomplished safely by transition to an adequate bisphosphonate regimen. For high- and very-high-risk patients, treating with osteoanabolic agents first, followed by antiresorptive agents, produces substantially larger BMD gains than the reverse treatment sequence, with the biggest differences seen for BMD of the hip. CONCLUSION: Awareness of the importance of treatment sequences can help improve osteoporosis care across the postmenopausal lifespan.
Subject(s)
Bone Density Conservation Agents , Diphosphonates , Humans , Bone Density Conservation Agents/therapeutic use , Female , Diphosphonates/therapeutic use , Osteoporosis, Postmenopausal/drug therapy , Denosumab/therapeutic use , Bone Density/drug effects , Osteoporosis/drug therapyABSTRACT
PURPOSE: Osteoporosis is under-diagnosed and often co-exists with other diseases. Very low bone mineral density (BMD) indicates risk of osteoporosis and opportunistic screening for low BMD in CT-scans has been suggested. In a non-contrast enhanced thoracic CT scan, the scan-field-of-view includes vertebrae enabling BMD estimation. However, many CT scans are obtained by administration of contrast material. If the impact of contrast enhancement on BMD measurements could be quantified, considerably more patients are eligible for screening. METHODS: This study investigated the impact of intravenous contrast on thoracic BMD measurements in cardiac CT scans pre- and post-contrast, including different contrast trigger levels of 130 and 180 Hounsfield units (HU). BMD was measured using quantitative CT with asynchronous calibration. RESULTS: In 195 participants undergoing cardiac CT (mean age 57±9 years, 37 % females) contrast increased mean thoracic BMD from 116±33 mg/cm3 (non-enhanced CT) to 130±38 mg/cm3 (contrast-enhanced CT) (p<0.001). Using clinical cut-off values for very low (<80 mg/cm3) and low BMD (<120 mg/cm3) showed that 24 % (47/195 participants) were misclassified when BMD was measured on contrast-enhanced CT-scans. Of the misclassified patients, 6 % (12/195 participants) were categorized as having low BMD despite having very low BMD on the non-enhanced images. Contrast-CT using a higher contrast trigger level showed a significant increase in BMD compared to the lower trigger level (119±32 vs. 135±40 mg/cm3, p<0.01). CONCLUSION: For patients undergoing cardiac CT, using contrast-enhanced images to assess BMD entails substantial overestimation. Contrast protocol trigger levels also affect BMD measurements. Adjusting for these factors is needed before contrast-enhanced images can be used clinically. MINI ABSTRACT: Osteoporosis is under-diagnosed. Contrast-enhanced CT made to examine other diseases might be utilized simultaneously for bone mineral density (BMD) screening. These scans, however, likely entails overestimation of BMD due to the effect of contrast. Adjusting for this effect is needed before contrast-enhanced images can be implemented clinically for BMD screening.
Subject(s)
Bone Diseases, Metabolic , Osteoporosis , Female , Humans , Middle Aged , Aged , Male , Bone Density , Absorptiometry, Photon/methods , Osteoporosis/diagnostic imaging , Tomography, X-Ray Computed/methods , Lumbar Vertebrae/diagnostic imaging , Retrospective StudiesABSTRACT
INTRODUCTION: Osteogenesis imperfecta (OI) is a rare genetic disease associated with multiple fractures throughout life. It is often treated with osteoporosis medications but their effectiveness at preventing fractures is unknown. The Treatment of Osteogenesis Imperfecta with Parathyroid Hormone and Zoledronic Acid trial will determine if therapy with teriparatide (TPTD) followed by zoledronic acid (ZA) can reduce the risk of clinical fractures in OI. METHODS AND ANALYSIS: Individuals aged ≥18 years with a clinical diagnosis of OI are eligible to take part. At baseline, participants will undergo a spine X-ray, and have bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) at the spine and hip. Information on previous fractures and previous bone targeted treatments will be collected. Questionnaires will be completed to assess pain and other aspects of health-related quality of life (HRQoL). Participants will be randomised to receive a 2-year course of TPTD injections 20 µg daily followed by a single intravenous infusion of 5 mg ZA, or to receive standard care, which will exclude the use of bone anabolic drugs. Participants will be followed up annually, have a repeat DXA at 2 years and at the end of study. Spine X-rays will be repeated at the end of study. The duration of follow-up will range between 2 and 8 years. The primary endpoint will be new clinical fractures confirmed by X-ray or other imaging. Secondary endpoints will include participant reported fractures, BMD and changes in pain and HRQoL. ETHICS AND DISSEMINATION: The study received ethical approval in December 2016. Following completion of the trial, a manuscript will be submitted to a peer-reviewed journal. The results will inform clinical practice by determining if TPTD/ZA can reduce the risk of fractures in OI compared with standard care. TRIAL REGISTRATION NUMBER: ISRCTN15313991.
Subject(s)
Bone Density Conservation Agents , Fractures, Bone , Osteogenesis Imperfecta , Humans , Adult , Adolescent , Zoledronic Acid/therapeutic use , Teriparatide/therapeutic use , Osteogenesis Imperfecta/complications , Osteogenesis Imperfecta/drug therapy , Bone Density Conservation Agents/therapeutic use , Quality of Life , Fractures, Bone/prevention & control , Fractures, Bone/complications , Bone Density , Pain/drug therapy , Randomized Controlled Trials as TopicABSTRACT
Buffered and effervescent alendronate (ALN-EFF) increases gastric pH and is reported to decrease the risk of gastrointestinal side effects compared to conventional formulations of alendronate (ALN). The clinical effectiveness of ALN-EFF, however, has not been investigated. This study aims to investigate if ALN-EFF is non-inferior to ALN in suppressing bone turnover markers (BTM). We conducted a 16-week prospective, randomized, open-label study comprising 64 postmenopausal women with BMD T-score < -1 naïve to osteoporosis treatment. Participants were randomized 1:1 to ALN or ALN-EFF. We collected blood samples at 0, 4, 8, and 16 weeks. Non-inferiority margin was determined as 12% (80% of efficacy retained), and an SD of 15% on change in CTx. CTx decreased by 58.2% ± 24.1% in the ALN group and by 46.9% ± 23.3% (CI - 38.42:- 55.35) in the ALN-EFF group (p = 0.08). The non-inferiority limit was 46.6%. With ALN-EFF the CI crosses the non-inferiority limit thus the test for non-inferiority was indeterminate. PINP decreased by 45.7 ± 22.6% in the ALN group and by 35.1 ± 20.7% in the ALN-EFF group (p = 0.07). Changes over time in the BTMs were not significantly different between the groups, p > 0.10 for both CTx and PINP. There was no difference in frequency of AEs or compliance between the two groups, but rate of discontinuation was lower with ALN-EFF. In conclusion, suppression of BTMs was not significantly different between the groups but formal non-inferiority could not be established.
Subject(s)
Bone Density Conservation Agents , Osteoporosis, Postmenopausal , Female , Humans , Alendronate/pharmacology , Osteoporosis, Postmenopausal/drug therapy , Prospective Studies , Bone Density , Bone Remodeling , Bone Density Conservation Agents/pharmacologyABSTRACT
PURPOSE: Weekly treatment with the intravenous glucocorticoid methylprednisolone for 12 weeks is mainstay in the treatment of Graves' orbitopathy but may decrease bone mass and impair bone structure. We therefore investigated bone turnover, -mass and -structure during the treatment cause in these patients. METHODS: We included 32 patients with Graves' orbitopathy scheduled for treatment with methylprednisolone. Bone turnover and thyroid function was measured at baseline and after 3, 9, 12, and 24 weeks, bone mineral density (BMD) was measured using dual x-ray absorptiometry at baseline and after 12 and 24 weeks, and bone structure was measured using high-resolution peripheral quantitative computed tomography at baseline and after 12 weeks. RESULTS: Bone turnover and tri-iodothyronine decreased throughout the study. Cortical volumetric BMD at both the radius and tibia increased significantly by 0.98 ± 0.38% (p = 0.01) and 1.35 ± 0.50% (p = 0.01), respectively and cortical porosity at both the radius and tibia decreased significantly by -7.67 ± 3.13% (p = 0.04) and -3.30 ± 2.17% (p = 0.04), respectively. Bone mineral density was stable during the first 12 weeks but increased significantly by 2.26 ± 3.61% at the femoral neck (p < 0.01) and by 2.24 ± 4.24% at the total hip towards week 24 (p = 0.02). Stratified analyses suggested that remission of hyperthyroidism was the most important determinant of changes in bone turnover, bone mass and structure. CONCLUSION: During a 12-week course of high-dose intravenous methylprednisolone bone turnover and cortical porosity decreased and during 24 weeks follow up bone mineral density increased. In terms of bone, methylprednisolone therefore is a safe treatment for Graves' orbitopathy.
Subject(s)
Graves Ophthalmopathy , Methylprednisolone , Humans , Graves Ophthalmopathy/diagnostic imaging , Graves Ophthalmopathy/drug therapy , Glucocorticoids/adverse effects , Bone Density , Bone RemodelingABSTRACT
PURPOSE OF REVIEW: The incretin hormones, glucagon like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP), have been shown to decrease bone resorption in humans. The aim of this review is to collate evidence and current advances in the research within the last year on the effect of incretins on skeletal health. RECENT FINDINGS: Preclinical studies show potential direct beneficial effects on bone by GLP-1 and GIP, however real world epidemiological data show no effects of GLP-1 receptor analogues on fracture risk. This may be due to the weight loss accompanied by GLP-1 treatment which may have detrimental effects on bone. GIP is shown to reduce bone resorption and increase bone formation. Further evidence suggests an additive effect of GIP and glucagon like peptide-2, which could affect bone by different mechanisms. SUMMARY: GIP and GLP-1 based therapies are more widespread used and may have potential beneficial effects on bone, possibly counterbalanced by weight loss. Long-term effects and side-effects of GIP or GIP/ GLP-2 co-administration remain to be elucidated, and longer term treatment trials are needed.
Subject(s)
Bone Resorption , Diabetes Mellitus, Type 2 , Humans , Incretins/therapeutic use , Gastric Inhibitory Polypeptide/therapeutic use , Glucagon-Like Peptide 1 , Bone Resorption/drug therapy , Glucagon-Like Peptide-1 Receptor , Weight Loss , Diabetes Mellitus, Type 2/complicationsABSTRACT
OBJECTIVES: To compare if the 4th and 5th metatarsophalangeal (MTP) joints evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT) could classify more patients with erosive rheumatoid arthritis (RA) compared with conventional radiography (CR) of the hands, wrists, and feet. Furthermore, we characterize and quantify bone erosions in the two MTP joints by HR-pQCT. METHODS: This single-center cross-sectional study included patients with established RA (disease duration ≥5 years). Blinded to patient data, the number and volume of erosions in the 4th and 5th MTP joints were measured by HR-pQCT, whereas the erosive scores by CR of 44 joints in the hands, wrists, and feet were assessed according to the Sharp/van der Heijde method. RESULTS: Among 42 participants, 30 patients were classified with erosive RA and 12 with non-erosive RA by CR. HR-pQCT of two MTP joints could classify more patients with erosive RA compared with CR of 44 joints (p = .03). The optimal cut-off value for the number and volume of erosions per patient in the 4th and 5th MTP joints by HR-pQCT was 7.5 erosions and 11.7 mm3 , respectively, for detecting erosive disease by CR. Erosions in the two MTP joints by HR-pQCT were found most frequently and were largest at the lateral quadrant of the 5th metatarsal head. CONCLUSION: The superiority of HR-pQCT of the 4th and 5th MTP joints compared with CR of 44 joints for classifying erosive RA provides a basis for larger studies evaluating if HR-pQCT could be used for diagnosing erosive RA in the future.
Subject(s)
Arthritis, Rheumatoid , Metatarsophalangeal Joint , Humans , Cross-Sectional Studies , Arthritis, Rheumatoid/diagnostic imaging , Tomography, X-Ray Computed/methods , Radiography , Metatarsophalangeal Joint/diagnostic imagingABSTRACT
CONTEXT: Zoledronate appears to reduce fracture rates in children with cerebral palsy (CP), but no previous randomized, controlled trial has been performed to compare the effect of zoledronate to placebo in children with CP. OBJECTIVE: To investigate the effect of zoledronate on bone mineral density (BMD) Z-scores in children with nonambulant CP in a randomized, controlled, double-blind trial. METHODS: Nonambulant children with CP (5 to 16 years of age) were randomized 1:1 to receive 2 doses of zoledronate or placebo at a 6-month interval. BMD Z-score changes at the lumbar spine and the lateral distal femur (LDF) were calculated from dual-energy x-ray absorptiometry scans. Monitoring included weight, bone age, pubertal staging, knee-heel length, adverse events, biochemical markers, and questionnaires. RESULTS: Twenty-four participants were randomized and all completed the study. Fourteen were assigned to zoledronate. The mean lumbar spine BMD Z-score increased 0.8 SD (95% CI: 0.4; 1.2) in the zoledronate group, which was significant when compared to 0.0 SD (95% CI: -0.3; 0.3) in the placebo group. Similarly, the LDF BMD Z-scores increased more in the zoledronate group. Severe acute phase symptoms affected 50% of the patients in the zoledronate group but were reported exclusively after the first dose. Growth parameters were similar in both groups. CONCLUSION: Zoledronate for 12 months increased BMD Z-scores significantly without affecting growth, but first-dose side effects were common and considerable. Studies into lower first doses and long-term outcomes are needed.
Subject(s)
Bone Density Conservation Agents , Cerebral Palsy , Humans , Child , Zoledronic Acid/therapeutic use , Bone Density , Diphosphonates/therapeutic use , Bone Density Conservation Agents/adverse effects , Cerebral Palsy/drug therapy , Imidazoles/adverse effects , Lumbar Vertebrae/diagnostic imagingABSTRACT
A giant cell tumour of bone presented in the os sacrum of a prepubertal girl. Surgery with reconstruction was performed, but total resection was impossible. Zoledronate failed to avoid tumour regrowth, and treatment was changed to denosumab, despite not being recommended for use in growing children. Denosumab treatment for 21 months reduced and stabilized tumour size, the girl became pain free with asymptomatic side effects as mild hypocalcemia, hypophosphatemia and sclerosis of newly formed bone.
ABSTRACT
OBJECTIVE: To review the comparative effectiveness of osteoporosis treatments, including the bone anabolic agents, abaloparatide and romosozumab, on reducing the risk of fractures in postmenopausal women, and to characterise the effect of antiosteoporosis drug treatments on the risk of fractures according to baseline risk factors. DESIGN: Systematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials. DATA SOURCES: Medline, Embase, and Cochrane Library to identify randomised controlled trials published between 1 January 1996 and 24 November 2021 that examined the effect of bisphosphonates, denosumab, selective oestrogen receptor modulators, parathyroid hormone receptor agonists, and romosozumab compared with placebo or active comparator. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials that included non-Asian postmenopausal women with no restriction on age, when interventions looked at bone quality in a broad perspective. The primary outcome was clinical fractures. Secondary outcomes were vertebral, non-vertebral, hip, and major osteoporotic fractures, all cause mortality, adverse events, and serious cardiovascular adverse events. RESULTS: The results were based on 69 trials (>80 000 patients). For clinical fractures, synthesis of the results showed a protective effect of bisphosphonates, parathyroid hormone receptor agonists, and romosozumab compared with placebo. Compared with parathyroid hormone receptor agonists, bisphosphonates were less effective in reducing clinical fractures (odds ratio 1.49, 95% confidence interval 1.12 to 2.00). Compared with parathyroid hormone receptor agonists and romosozumab, denosumab was less effective in reducing clinical fractures (odds ratio 1.85, 1.18 to 2.92 for denosumab v parathyroid hormone receptor agonists and 1.56, 1.02 to 2.39 for denosumab v romosozumab). An effect of all treatments on vertebral fractures compared with placebo was found. In the active treatment comparisons, denosumab, parathyroid hormone receptor agonists, and romosozumab were more effective than oral bisphosphonates in preventing vertebral fractures. The effect of all treatments was unaffected by baseline risk indicators, except for antiresorptive treatments that showed a greater reduction of clinical fractures compared with placebo with increasing mean age (number of studies=17; ß=0.98, 95% confidence interval 0.96 to 0.99). No harm outcomes were seen. The certainty in the effect estimates was moderate to low for all individual outcomes, mainly because of limitations in reporting, nominally indicating a serious risk of bias and imprecision. CONCLUSIONS: The evidence indicated a benefit of a range of treatments for osteoporosis in postmenopausal women for clinical and vertebral fractures. Bone anabolic treatments were more effective than bisphosphonates in the prevention of clinical and vertebral fractures, irrespective of baseline risk indicators. Hence this analysis provided no clinical evidence for restricting the use of anabolic treatment to patients with a very high risk of fractures. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019128391.