Clinical Fracture Research Articles

Duration of Adjuvant Aromatase-Inhibitor Therapy in Postmenopausal Breast Cancer

BackgroundFor postmenopausal women with hormone-receptor–positive breast cancer, the most effective duration for adjuvant therapy with an aromatase inhibitor remains unclear.MethodsIn this prospective, phase 3 trial, we randomly assigned postmenopausal women with hormone-receptor–positive breast cancer who had received 5 years of adjuvant endocrine therapy to receive the aromatase inhibitor anastrozole for an additional 2 years (2-year group, receiving a total of 7 years) or an additional 5 years (5-year group, receiving a total of 10 years). The primary end point was disease-free survival. The primary analysis included all the patients who were still participating in the trial and who had no recurrence 2 years after randomization (i.e., when treatment in the 2-year group had ended). Secondary end points were overall survival, contralateral breast cancer, second primary cancer, and clinical bone fracture.ResultsAmong the 3484 women who were enrolled in the trial, 3208 remained in the trial without disease progression after the first 2 years of extended anastrozole treatment following randomization. Among these women, disease progression or death occurred in 335 women in each treatment group in the primary-analysis set at 8 years (hazard ratio, 0.99; 95% confidence interval [CI], 0.85 to 1.15; P=0.90). No between-group differences occurred in most secondary end points, and subgroup analyses did not indicate differences in any particular subgroup. The risk of clinical bone fracture was higher in the 5-year group than in the 2-year group (hazard ratio, 1.35; 95% CI, 1.00 to 1.84).ConclusionsIn postmenopausal women with hormone-receptor–positive breast cancer who had received 5 years of adjuvant endocrine therapy, extending hormone therapy by 5 years provided no benefit over a 2-year extension but was associated with a greater risk of bone fracture. (Funded by AstraZeneca and the Austrian Breast and Colorectal Cancer Study Group; ABCSG-16/SALSA ClinicalTrials.gov number, NCT00295620.)

Current concept management of talus fracture: a literature review

Fractures of the talus are uncommon. The relative infrequency of these injuries relates to limited guidelines to treat talus fracture. Talus fracture is always associated with high energy injury critical to the normal function of the ankle, subtalar, and transverse tarsal joints. Outcomes vary widely and are related to the degree of initial fracture displacement. Nondisplaced fractures have a favorable outcome in most cases. Failure to recognize fracture displacement (even when minimal) can lead to undertreatment and poor outcomes. Current detailed diagnoses through Multidetector CT (MDCT) are preferred to avoid miss diagnosed in talar fracture. Although early treatment and delayed treatment did not significantly differ, multiple-choice to treat talus fracture should be known. Conservative and operative treatment can be done in accordance with clinical findings and fracture patterns. With a high risk of complication, appropriate therapy should be done. Many research and articles have been done to develop the treatment and reduce complications over talar fracture from an invasive procedure to a non-invasive procedure like arthroscopy. Therefore, we compile current treatment to give another perspective for surgeons to treat talar fracture patients

Bringing Mechanical Context to Image-Based Measurements of Bone Integrity.

Image-based measurements of bone integrity are used to estimate failure properties and clinical fracture risk. This paper (1) reviews recent imaging studies that have enhanced our understanding of the mechanical pathways to bone fracture and (2) discusses the influence that inter-individual differences in image-based measurements may have on the clinical assessment of fracture risk RECENT FINDINGS: Increased tissue mineralization is associated with improved bone strength but reduced fracture toughness. Trabecular architecture that is important for fatigue resistance is less important for bone strength. The influence of porosity on bone failure properties is heavily dependent on pore location and size. The interaction of various characteristics, such as bone area and mineral content, can further complicate their influence on bone failure properties. What is beneficial for bone strength is not always beneficial for bone toughness or fatigue resistance. Additionally, given the large amount of imaging data that is clinically available, there is a need to develop effective translational strategies to better interpret non-invasive measurements of bone integrity.

Low-dose oral glucocorticoid therapy and risk of osteoporotic fractures in patients with rheumatoid arthritis: a cohort study using the Clinical Practice Research Datalink.

ObjectivesClinical trials have shown that low-dose glucocorticoid therapy in patients with RA reduces bone loss in hands or hip, but the effect on osteoporotic fractures is not yet clear. Therefore, we investigated the use of low-dose oral glucocorticoids and risk of osteoporotic fractures among patients with RA.MethodsThis was a cohort study including patients with RA aged 50+ years from the Clinical Practice Research Datalink between 1997 and 2017. Exposure to oral glucocorticoids was stratified by the most recent prescription in current (<6 months), recent (7–12 months) and past (>1 year) use, and average daily and cumulative doses. Risk of incident osteoporotic fractures (including hip, vertebrae, humerus, forearm, pelvis and ribs) was estimated by time-dependent Cox proportional-hazards models, adjusted for lifestyle parameters, comorbidities and comedications. Secondary analyses assessed osteoporotic fracture risk with a combination of average daily and cumulative doses of oral glucocorticoids.ResultsAmong 15 123 patients with RA (mean age 68.8 years, 68% females), 1640 osteoporotic fractures occurred. Current low-dose oral glucocorticoid therapy (≤7.5 mg prednisolone equivalent dose/day) in patients with RA was not associated with overall risk of osteoporotic fractures (adjusted hazard ratio 1.14, 95% CI 0.98, 1.33) compared with past glucocorticoid use, but was associated with an increased risk of clinical vertebral fracture (adjusted hazard ratio 1.59, 95% CI 1.11, 2.29). Results remained unchanged regardless of a short-term or a long-term use of oral glucocorticoids.ConclusionClinicians should be aware that even in RA patients who receive low daily glucocorticoid doses, the risk of clinical vertebral fracture is increased.

Meta-Analysis of Clinical Fracture Risk Reduction of Antiosteoporosis Drugs: Direct and Indirect Comparisons and Meta-Regressions

ObjectiveAntiosteoporotic drug (AOD) trials have variabilities in duration and fracture risks. This study evaluated AOD’s versus controls regarding reduction in relative rates and rate differences in vertebral and hip fractures and comparative costs. MethodsPrimary randomized controlled trials of antiosteoporotic drugs in postmenopausal women with documentation of vertebral fracture rates or hip fracture rates were extracted from meta-analyses and PubMed through February 2021. Direct and indirect meta-analyses and meta-regressions analyzed the fracture reductions. ResultsThere were 24 randomized controlled trials of drug versus placebo (73 862 women) and 10 randomized controlled trials of drug versus drug. The reductions in the relative rates of vertebral fractures were significant for antiresorptive (alendronate, risedronate, zoledronate, denosumab, and raloxifene) and anabolic (teriparatide, abaloparatide, and romosozumab) drugs. Denosumab, teriparatide, and abaloparatide were more effective in reducing vertebral fracture rates than oral bisphosphates (all P < .05) but were not more effective in reducing vertebral fracture rates than zoledronate. The reductions in hip fracture rates were significant for alendronate, denosumab, and zoledronate (all P < .05), without significant differences among drugs. Anabolic drugs did not show significant hip fracture rate reduction. Meta-regression of rate differences enabled the calculation of costs per vertebral fracture prevented, which were estimated at >$100 000 for anabolic drugs and between $2289 and $28 947 for antiresorptive drugs. Many direct drug versus drug trials were underpowered to demonstrate benefits of one drug over another. ConclusionThis study suggests goal-directed, cost-effective therapies relative to patient risk for vertebral and hip fractures. Anabolic drugs are better at preventing vertebral fractures than oral bisphosphonates. Anabolic drugs are not superior to zoledronate or denosumab and are substantially more expensive. When comparing drugs that prevented hip fractures, there was no statistical benefit of any drug.

Assessment of site-specific X-ray procedure codes for fracture ascertainment: a registry-based cohort study.

Real-world evaluation of fracture epidemiology at the population level from electronic healthcare information, such as administrative data, requires comprehensive data sources and validated case definitions. Only hip fractures are routinely hospitalized, and the identification of most osteoporosis-related fractures which are non-hospitalized fractures remains challenging. Plain X-rays (radiographs) are first-line tests for fracture diagnosis and are frequently repeated to monitor fracture healing, and claims data related to radiologic procedures are available in many healthcare systems. We hypothesized that temporal clustering in plain X-ray procedure codes might be an ancillary source of fracture data. We identified individuals age 40years and older in Manitoba Bone Mineral Density (BMD) Registry with a fracture diagnosis (hip, forearm, humerus, clinical vertebral) before or following a BMD test. A subset underwent detailed review of X-rays to verify an acute fracture. We examined the association between fracture diagnosis and numbers of site-specific X-ray procedures. The registry cohort included 7793 individuals with a fracture in the previous 5years and 8417 incident fractures. The X-ray review cohort included 167 radiologically-verified fractures. The number of site-specific X-ray codes was greater in those with vs without fracture (all P < 0.001). The number of days with site-specific X-rays was strongly associated with a fracture diagnosis (area under the curve 0.90 to 0.99 for all non-vertebral fractures, 0.66 to 0.75 for clinical vertebral fractures). There was good agreement between the date of fracture diagnosis and the first X-ray at all non-vertebral fracture sites (Spearman correlation range 0.65 to 0.99), but this was lower for clinical vertebral fractures (range 0.29 to 0.59). Temporal clustering in site-specific X-ray procedures was associated with a corresponding fracture diagnosis in administrative medical records. Non-vertebral fracture sites were more strongly associated with X-ray procedures than clinical vertebral fractures.

Pharmacological interventions versus placebo, no treatment or usual care for osteoporosis in people with chronic kidney disease stages 3-5D.

Chronic kidney disease (CKD) is an independent risk factor for osteoporosis and is more prevalent among people with CKD than among people who do not have CKD. Although several drugs have been used to effectively treat osteoporosis in the general population, it is unclear whether they are also effective and safe for people with CKD, who have altered systemic mineral and bone metabolism. To assess the efficacy and safety of pharmacological interventions for osteoporosis in patients with CKD stages 3-5, and those undergoing dialysis (5D). We searched the Cochrane Kidney and Transplant Register of Studies up to 25 January 2021 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. Randomised controlled trials comparing any anti-osteoporotic drugs with a placebo, no treatment or usual care in patients with osteoporosis and CKD stages 3 to 5D were included. Two review authors independently selected studies, assessed their quality using the risk of bias tool, and extracted data. The main outcomes were the incidence of fracture at any sites; mean change in the bone mineral density (BMD; measured using dual-energy radiographic absorptiometry (DXA)) of the femoral neck, total hip, lumbar spine, and distal radius; death from all causes; incidence of adverse events; and quality of life (QoL). Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Seven studies involving 9164 randomised participants with osteoporosis and CKD stages 3 to 5D met the inclusion criteria; all participants were postmenopausal women. Five studies included patients with CKD stages 3-4, and two studies included patients with CKD stages 5 or 5D. Five pharmacological interventions were identified (abaloparatide, alendronate, denosumab, raloxifene, and teriparatide). All studies were judged to be at an overall high risk of bias. Among patients with CKD stages 3-4, anti-osteoporotic drugs may reduce the risk of vertebral fracture (RR 0.52, 95% CI 0.39 to 0.69; low certainty evidence). Anti-osteoporotic drugs probably makes little or no difference to the risk of clinical fracture (RR 0.91, 95% CI 0.79 to 1.05; moderate certainty evidence) and adverse events (RR 0.99, 95% CI 0.98 to 1.00; moderate certainty evidence). We were unable to incorporate studies into the meta-analyses for BMD at the femoral neck, lumbar spine and total hip as they only reported the percentage change in the BMD in the intervention group. Among patients with severe CKD stages 5 or 5D, it is uncertain whether anti-osteoporotic drug reduces the risk of clinical fracture (RR 0.33, 95% CI 0.01 to 7.87; very low certainty evidence). It is uncertain whether anti-osteoporotic drug improves the BMD at the femoral neck because the certainty of this evidence is very low (MD 0.01, 95% CI 0.00 to 0.02). Anti-osteoporotic drug may slightly improve the BMD at the lumbar spine (MD 0.03, 95% CI 0.03 to 0.04, low certainty evidence). No adverse events were reported in the included studies. It is uncertain whether anti-osteoporotic drug reduces the risk of death (RR 1.00, 95% CI 0.22 to 4.56; very low certainty evidence). Among patients with CKD stages 3-4, anti-osteoporotic drugs may reduce the risk of vertebral fracture in low certainty evidence. Anti-osteoporotic drugs make little or no difference to the risk of clinical fracture and adverse events in moderate certainty evidence. Among patients with CKD stages 5 and 5D, it is uncertain whether anti-osteoporotic drug reduces the risk of clinical fracture and death because the certainty of this evidence is very low. Anti-osteoporotic drug may slightly improve the BMD at the lumbar spine in low certainty evidence. It is uncertain whether anti-osteoporotic drug improves the BMD at the femoral neck because the certainty of this evidence is very low. Larger studies including men, paediatric patients or individuals with unstable CKD-mineral and bone disorder are required to assess the effect of each anti-osteoporotic drug at each stage of CKD.

Fracture recurrence in hip fracture with menopausal hormone therapy versus risedronate: a clinical trial

Objectives An open-label, randomized trial was conducted to examine the effects of risedronate versus menopausal hormone therapy (MHT) in postmenopausal women with recent hip fracture. Methods Among 1165 eligible women, 281 were recruited and randomly assigned to receive oral risedronate (35 mg/week) or percutaneous estradiol gel (1.5 mg/day) plus oral micronized progesterone (100 mg/day) for 4 years. The primary end point was recurrent fracture and the secondary end points were mortality and bone mineral density (BMD). Results Kaplan–Meier analyses showed no significant differences in fracture recurrence and mortality between the two groups. The incidence of any new fracture per 100 person-years (PY) was 8.63 in the risedronate group and 12.86 in the MHT group (p = 0.180); that of clinical fracture was 4.75 and 6.99, respectively (p = 0.265); and that of asymptomatic vertebral fracture was 4.87 and 5.58, respectively (p = 0.764). The respective incidence of death per 100 PY was 3.58 and 4.40 (p = 0.503). BMD increased comparably at the lumbar spine in both groups. BMD at the total hip did not change in the risedronate group, but increased significantly by 2.8% in the MHT group. Conclusions MHT might not differ from risedronate in the prevention of secondary fractures and death among postmenopausal women with recent hip fracture.

High bone mass phenotype in a cohort of patients with Osteogenesis Imperfecta caused due to BMP1 and C-propeptide cleavage variants in COL1A1

ObjectivesOsteogenesis Imperfecta (OI) is a heterogeneous condition mainly characterised by bone fragility; extra-skeletal features in OI include blue sclerae, dentinogenesis imperfecta, skin laxity and joint hyper-extensibility. Most patients with OI are thought to have a low bone mass but contrary to expectations there are certain forms of OI with high bone mass which this study explores in further detail. MethodA cohort of n = 6 individuals with pathogenic variants in BMP1 and the C-propeptide cleavage variants in COL1A1 were included in this study. Detailed clinical and radiological phenotyping was done and correlated with genotype to identify patterns of clinical presentation and fracture history in this cohort of patients. This data was compared to previously reported literature in this group. Results2 patients with BMP1 and 4 patients with pathogenic variants in C-propeptide region in COL1A1 were deep-phenotyped as part of this study and 1 patient with C-propeptide variant in COL1A1, showed low bone mineral density. In those with an elevated bone mineral density, this became even more apparent on bisphosphonate therapy. Patients in this cohort had variable clinical presentation ranging from antenatal presentation to more of an insidious course resulting in later confirmation of genetic diagnosis up to 19 years of age. ConclusionsPatients with pathogenic variants in the C-propeptide region of COL1A1/A2 and BMP1 appear to have a high bone mass phenotype with increased sensitivity to bisphosphonate therapy. It is important to closely monitor patients with these genotypes to assess their response to therapy and tailor their treatment regime accordingly.

Incidence of fractures among patients receiving medications for type 2 diabetes or chronic obstructive pulmonary disease and glucocorticoid users according to the National Claims Database in Japan

SummaryAccording to information from the National Health Insurance and Claims database, the risk for hip, radius, and clinical vertebral fractures was higher among patients receiving medication for type 2 diabetes, COPD, or glucocorticoids than among the whole Japanese population after middle age.PurposeThe aim of this study was to determine the incidence of fractures among patients receiving medications for type 2 diabetes or chronic obstructive pulmonary disease (COPD) and using glucocorticoids (GC) according to the National Database of Health Insurance Claims (NDB) in Japan.MethodsWe obtained data on the number of fractures and patients receiving medications for type 2 diabetes, COPD, or GC from the NDB. The claims data included sex, age group, injury/illness name, hospitalization, outpatient, surgery/medical treatment, and drugs used between January and December 2017.ResultsThe risk of hip fracture was higher among patients receiving medications for diabetes or COPD and GC users than in the Japanese population, with standardized incidence ratios (SIRs) of 1.71 (95% confidence interval [CI]1.6–1.75), 1.35 (95% CI 1.28–1.42), and 1.62 (95% CI 1.53–1.71) in men and 1.81 (95% CI 1.79–1.84), 1.67 (95% CI 1.54–1.80), and 1.71 (95% CI 1.66–1.76) in women, respectively. There was also a significantly higher incidence of radial fractures in women and clinical vertebral fractures in both men and women. A greater risk of hip fracture was found among diabetic patients starting in their late 40 s.ConclusionsReal-world data revealed that the incidence of hip, radius, and clinical vertebral fractures was significantly higher among patients receiving medications for diabetes or COPD and GC users than in the Japanese population after middle age.

Teriparatide Treatment in Patients with Pregnancy- and Lactation-Associated Osteoporosis

Pregnancy- and lactation-associated osteoporosis (PLO) is a rare disease, presenting in most cases with severe back pain due to low energy vertebral fractures (VFs). Our purpose was to assess the effect of teriparatide (TPTD) vs. conventional management on areal bone mineral density (aBMD) and trabecular bone score (TBS) in patients with PLO. A multicenter retrospective cohort study concerning premenopausal women with PLO. Nineteen women were treated with TPTD (20μg/day) (group A) plus calcium and vitamin D and eight women with calcium and vitamin D only (group B) for up to 24months. The primary end-point was between group differences in lumbar spine (LS) and total hip (TH) aBMD, and TBS at 12 and 24months. Patients in group A had sustained a median of 4.0 VFs (3-9) vs. 2.5 VFs (1-10) in group B (p = 0.02). At 12months, patients on TPTD vs. controls achieved a mean aBMD increase of 20.9 ± 11.9% vs. 6.2 ± 4.8% at the LS (p < 0.001), 10.0 ± 11.6% vs. 5.8 ± 2.8% at the TH (p = 0.43), and 6.7 ± 6.9% vs. 0.9 ± 3.7% in TBS (p = 0.09), respectively. At 24months, seven patients on TPTD and six controls achieved a mean LS aBMD increase of 32.9 ± 13.4% vs. 12.2 ± 4.2% (p = 0.001). P1NP levels during the first month of TPTD treatment were positively correlated with the 1-year LS aBMD change (r = 0.68, p = 0.03). No new clinical fractures occurred while on-treatment. In patients with PLO, TPTD treatment resulted in significantly greater increases in LS aBMD compared with calcium and vitamin D supplementation at 12 and 24months.

Risk of Subsequent Fractures in Postmenopausal Women After Nontraumatic vs Traumatic Fractures

The burden of fractures among postmenopausal women is high. Although nontraumatic fractures are strong risk factors for future fracture, current clinical guidelines do not address traumatic fractures. To determine how future fracture risk varies according to whether an initial fracture is traumatic or nontraumatic. We conducted a prospective observational study using data from the Women's Health Initiative Study (WHI) (enrollment, September 1994-December 1998; data analysis, September 2020 to March 2021), which enrolled postmenopausal women aged 50 to 79 years at baseline at 40 US clinical centers. The WHI Clinical Trials and WHI Bone Density Substudy, conducted at 3 of the clinical centers, asked participants to report the mechanism of incident fractures. Of 75 335 participants, information regarding incident fracture and covariates was available for 66 874 participants (88.8%), who comprised the analytic sample of this study. Mean (SD) follow-up was 8.1 (1.6) years. None. Incident clinical fractures were self-reported at least annually and confirmed using medical records. Participants reported the mechanism of incident fracture as traumatic or nontraumatic. Among the 66 874 participants in the analytic sample (mean [SD] age, 63.1 [7.0] years and 65.3 [7.2] years among women without and with clinical fracture, respectively), 7142 participants (10.7%) experienced incident fracture during the study follow-up period. The adjusted hazard ratio (aHR) of subsequent fracture after initial fracture was 1.49 (95% CI, 1.38-1.61). Among women whose initial fracture was traumatic, the association between initial fracture and subsequent fracture was significantly increased (aHR, 1.25; 95% CI, 1.06-1.48). Among women whose initial fracture was nontraumatic, the association between initial fracture and subsequent fracture was also increased (aHR, 1.52; 95% CI, 1.37-1.68). Confidence intervals for associations between initial fracture and subsequent fracture were overlapping for traumatic and nontraumatic initial fracture strata. In this cohort study, among postmenopausal women older than 50 years, fracture was associated with a greater risk of subsequent fracture regardless of whether the fracture was traumatic or nontraumatic. These findings suggest that clinical osteoporosis assessment should include high-trauma as well as low-trauma fractures.

POS0171 UNDERESTIMATION OF THE FRACTURE RISK BY THE FRAX FORMULA IN CHRONIC GLUCOCORTICOID USERS: A 10-YEAR LONGITUDINAL VALIDATION STUDY

Background:Objectives:To compare the actual fracture incidence over 10 years in a longitudinal cohort of patients using glucocorticoids (GCs) with the risk prediction from FRAX (fracture risk assessment tool).Methods:Patients who attended our out-patient rheumatology clinics were included according to the following criteria: (1) adult patients ≥18 years; (2) underlying rheumatic diseases requiring prednisolone treatment (≥5mg/day); and (3) have had a DXA scan (baseline) performed between years 2007-2009. The predicted rates of major osteoporotic and hip fractures were estimated using FRAX (China database) based on the clinical data at the time of DXA, with adjustment when daily dose of prednisolone ≥7.5mg (multiply by 1.15 for major osteoporotic and 1.20 for hip fracture). The actual observed incidence of symptomatic vertebral and non-vertebral fractures at 10 years (in years 2017-2019) follow-up was retrieved by medical record review and compared with the estimated rates by FRAX. Factors associated with symptomatic clinical fractures at 10 years were studied by logistic regression.Results:89 patients were studied (age 49.3±8.8 years at DXA examination; 98% women). The underlying rheumatic diseases were systemic lupus erythematosus (69%), rheumatoid arthritis (17%) and others (14%). The mean daily dose of prednisolone at baseline was 7.7±6.5mg (38% patients had daily dose ≥7.5mg). History of personal fracture was present in 4(4.5%) patients and 22% of female patients had menopause before the age of 45 years. The mean body mass index (BMI) was 23.5±3.3kg/m2 (4.5% ≤18kg/m2). Osteoporosis (bone mineral density [BMD] T score ≤-2.5) of the hip, femoral neck and lumbar spine occurred at a frequency of 11.2%, 13.5% and 25.8%, respectively at baseline (32% at any of the 3 sites). 30(34%) patients received anti-osteoporotic treatment (oral bisphosphonates in 25, raloxifene in 3 and denosumab in 2 patients). The estimated mean 10-year risk of major osteoporotic and hip fractures using the BMD data and other risk factors in the FRAX formula, adjusted for prednisolone dose, was 4.3% and 1.0%, respectively. After a follow-up of 10 years, one patient had a hip fracture, 3 patients had humerus fractures and 9 patients had symptomatic vertebral fractures. The actual observed major osteoporotic and hip fracture incidence was 14.6% and 1.1%, respectively (0.146 and 0.011 per 10 patient-years). The observed major clinical fracture rate was significantly higher than that estimated by FRAX (14.6% vs 4.3%; p=0.04). Logistic regression revealed that the only factor independently associated with major clinical fracture at 10 years was BMD T score ≤-2.5 at spine, hip or femoral neck at baseline (OR7.11[1.73-29.2]; p=0.007). Age, prednisolone daily dose, BMI, history of fracture, chronic smoking, having underlying SLE vs not and early menopause were not significantly associated with new clinical fractures.Conclusion:Despite adjustment for prednisolone dosage, the FRAX formula underestimates the major clinical fracture risk in patients using long-term GCs. The deleterious effect of GCs on bone quality, high proportion of SLE patients, disease activity and use of additional doses of GCs and other immunosuppressive drugs during follow-up are among the contributing factors for this underestimation.Disclosure of Interests:None declared

Patellar Fracture Fixation With Cannulated Compression Screws and FiberTape Cerclage

Transverse patella fractures with loss of knee extensor mechanism function are a common orthopaedic injury requiring operative fixation. Current accepted surgical options for noncomminuted transverse fractures include open reduction with tension band wiring. Although these procedures result in good clinical outcomes and fracture healing, symptomatic hardware from the historically used metal implants is very common. The purpose of this Technical Note is to describe a technique for treatment of transverse patellar fractures using cannulated compression screws with tensioned high-resistance suture tape functioning as the tension band. This technique provides effective, reproducible fracture fixation while minimizing symptomatic hardware, failure, and reoperation.

Hypercalcemia in a Patient Treated With Abaloparatide

Abstract Introduction: The antifracture efficacy of newer agents like PTHrP analogues is promising but knowledge about the mechanism of action and safety profile is needed in order to use these agents effectively. The reported incidence of hypercalcemia defined as albumin-adjusted serum calcium ≥10.7mg/dL was 3.4% in Abaloparitide. Case Presentation: A 59 year-old female with past medical history significant for diabetes mellitus type 2, hypothyroidism, necrotizing autoimmune myositis, osteoporosis and renal stones presented with complaints of generalized body aches and pains with swelling and redness of the left leg. The patient was diagnosed with osteoporosis based on atraumatic L4 compressive injury involving superior end plate. Her only DXA scan was 8 years ago which showed osteopenia, with the lowest T score of -1.2 at lumbar spine. Subsequent evaluation with DXA scan was unable to be performed due to physical disabilities. She was intolerant to oral bisphosphonates and was started on abaloparatide subcutaneous injections 2 weeks prior to her current admission. Her physical examination was positive for obesity, proximal muscle weakness and bilateral leg edema with bruises and left leg erythema. Laboratory findings showed hypercalcemia with corrected calcium levels of 12.48 mg/dl, suppressed intact PTH 4 pg/ml. Evaluations for secondary causes of hypercalcemia were negative. Her last dose of abaloparatide injection was the morning prior to her presentation to the emergency room. The patient was treated with IV fluids and her calcium level improved within 24 hours with normalization of intact PTH level in 72hrs. Abaloparatide injection was suspended on admission. Hypercalcemia with suppressed PTH was most likely secondary to abaloparatide given the timing of the hypercalcemia after the injection and resolution of hypercalcemia and normalization of PTH. Conclusions: Abaloparatide is a peptide that selectively binds to the RG conformation of the parathyroid hormone type 1 receptor. Abaloparatide is increasingly used following the results from the ACTIVE and ACTIVExtend trials which demonstrate significant increase in bone mineral density and risk reduction of vertebral, nonvertebral, clinical, and major osteoporotic fractures. Hypercalcemia was reported as a side effect, but there is no guidance on further evaluation or management of these patients. The incidence of hypercalcemia defined as albumin-adjusted serum calcium ≥10.7mg/dL is 3.4 % and risk is increased in patients with renal impairment. As in our case, transient hypercalcemia and PTH suppression may be associated with abaloparatide. Efficacy of abaloparatide and impact on bone density with delay or interrupted treatment are not available. Further studies are needed to guide monitoring and treatment of clinically symptomatic transient hypercalcemia in patients taking abaloparatide.

Recurrent Atraumatic Pelvic Fractures in a Patient With Cushing’s Disease - Is DEXA Scan Really Useful to Predict the Future Fracture Risk?

Background: Cushing’s disease may present with a variety of clinical features, including osteoporosis and fracture. Due to the inhibitory effects of cortisol on osteoblastic activity and enhancing effects on osteoclastic activity, these patients are more prone to have osteoporotic fractures. We report a case of ACTH dependent Cushing’s disease presenting with recurrent atraumatic pelvic fractures in a woman despite normal bone mineral density for her age. Clinical Case: A 56 year-old-woman was referred to the endocrinology department for suspected Cushing’s syndrome following a recent atraumatic fracture of right pubic ramus. She had a history of weight gain and easy fatigue. On examination, she had subtle changes suggestive of Cushing’s syndrome, including mild truncal obesity, minimal bruising and moon face. She had been taking hormone replacement therapy for 3 years for the post-menopausal symptoms. Her bone mineral density was normal for her age on a recent DEXA scan [femoral neck T score: -0.9, Z score: 0.1, lumbar spine (L1-L4) T score: -1.2, Z score: -0.1]. Her vitamin D, serum calcium and parathyroid hormone levels were normal. Her 24-hour urinary cortisol was 688 nmol/day (reference range: <200 nmol/day), low dose dexamethasone suppression cortisol 525 nmol/L (reference range: <50 nmol/day), ACTH 96 ng/L (reference range: <50 ng/L), indicating ACTH dependent Cushing syndrome. MRI pituitary showed 7 mm right sided hypoenhancing area suggestive of a pituitary microadenoma. CT neck, thorax, abdomen and pelvis did not show any source of ectopic ACTH secretion but did show generalised osteopenia, with old fractures of the ribs and left ilium. She was referred for trans-sphenoidal resection of pituitary tumour. While awaiting pituitary surgery she was treated with metyrapone: at this time she suffered a further atraumatic fracture of the left pubic ramus. Conclusion: Glucocorticoid excess predominantly affects trabecular bones (pelvis, ribs, lumbar spine) as compared to cortical bones. Due to micro-architectural changes, reduction in bone strength is disproportionately greater than would be expected from BMD measured by DEXA. Clinicians should be aware that recurrent fracture of trabecular bones may indicate Cushing’s disease even though other clinical features of cortisol excess are minimal or absent.

Effects of Myo-inositol Hexaphosphate (SNF472) on Bone Mineral Density in Patients Receiving Hemodialysis: An Analysis of the Randomized, Placebo-Controlled CaLIPSO Study.

In the CaLIPSO study, intravenous administration of SNF472 (300 or 600 mg) during hemodialysis significantly attenuated progression of coronary artery and aortic valve calcification. SNF472 selectively inhibits formation of hydroxyapatite, the final step in cardiovascular calcification. Because bone mineral is predominantly hydroxyapatite, we assessed changes in bone mineral density in CaLIPSO. Patients with coronary artery calcification at screening (Agatston score of 100-3500 U) were randomized 1:1:1 to receive placebo, 300 mg SNF472, or 600 mg SNF472 as an intravenous infusion during hemodialysis three times weekly for 52 weeks. Dual-energy x-ray absorptiometry (DXA) scans were obtained at baseline (screening) and end of treatment, and between-group changes from baseline were compared using analysis of covariance. Among 274 randomized patients, 202 had evaluable DXA scans at baseline and postrandomization (the DXA-modified intention-to-treat population). Mean (95% confidence interval) changes in total-hip bone mineral density from baseline to week 52 were -1.5% (-2.7% to -0.3%), -1.5% (-2.7% to -0.4%), and -2.5% (-3.8% to -1.2%) in the placebo, 300 mg SNF472, and 600 mg SNF472 groups, respectively. Mean (95% confidence interval) changes in femoral-neck bone mineral density from baseline to week 52 were -0.3% (-1.6% to 1.0%), -1.0% (-2.3% to 0.2%), and -2.6% (-4.0% to -1.3%), respectively. Regression analyses showed no correlation between change in coronary artery calcium volume and change in bone mineral density at either location. Changes in serum alkaline phosphatase, calcium, magnesium, phosphate, and intact parathyroid hormone levels were similar across treatment groups. Clinical fracture events were reported for four of 90, three of 92, and six of 91 patients in the placebo, 300 mg SNF472, and 600 mg SNF472 groups, respectively. Bone mineral density decreased modestly in all groups over 1 year. In the 600 mg SNF472 group, the reduction appeared more pronounced. Reported fractures were infrequent in all groups. Effect of SNF472 on Progression of Cardiovascular Calcification in End-Stage-Renal-Disease (ESRD) Patients on Hemodialysis (HD), NCT02966028.

Zoledronic acid reduces the rate of clinical fractures after surgical repair of a hip fracture regardless of the Pretreatment bone mineral density.

Zoledronic acid reduces the risk of subsequent fractures after repair of a hip fracture. It is still unclear whether the benefits in fracture reduction with ZA depend upon hip bone mineral density at the time of fracture. We preformed additional post hoc analyses of data from the HORIZON Recurrent Fracture Trial to determine if ZA treatment reduced the risk of new clinical fractures regardless of pretreatment BMD. We modeled femoral neck and total hip BMD as both continuous and dichotomous variables (BMD T-score above and below -2.5). There are no evidence that baseline femoral neck and total hip BMD modified the anti-fracture efficacy of ZA when pretreatment BMD was analyzed as a continuous or a dichotomous variable (interaction p-values > 0.20). The clinical fracture efficacy of ZA was similar among patients with pretreatment femoral neck BMD values above and below -2.5 (relative hazards = 0.60 and 0.67, respectively, interaction p-value = 0.95). A similar result was obtained using pretreatment total hip BMD values (relative hazards = 0.72 and 0.57, respectively, interaction p-value = 0.41). There data should provide more comfort in prescribing ZA after surgical repair of a hip fracture, regardless of pretreatment BMD.

Relationship between the Depth of Penetration and Fracture Resistance of Various Sealers: A Comparative Study

The aim of this in vitro study was to estimate the penetration depth and fracture resistance of three different sealers and to verify the relationship between the penetration depth and fracture resistance. Sixty single-rooted teeth were selected and root canal preparation was done. After the instrumentation, the teeth were divided into three groups of 20 each. The groups were then obturated with gutta-percha (GP)-AH Plus sealer, Resilon-Real Seal, and propoint-bioceramic sealers, respectively. Ten teeth from each group were sectioned at three different regions (i.e., coronal, middle, and apical thirds of the root canal) and were viewed under a confocal microscope to determine the penetration depth of the sealer. The remaining samples were subjected to fracture resistance under a universal testing machine and the statistical analysis was done by using one-way ANOVA and post hoc Bonferroni tests. Propoint-bioceramic group showed the highest fracture resistance values followed by GP-AH Plus sealer and Resilon-Real seal groups with no significant difference noticed between them. Depth of penetration was greater for GP-AH Plus sealer, propoint-bioceramic, with no significant difference followed by the Resilon-Real seal group. The newer obturating material propoint-bioceramic group showed a greater fracture resistance. No correlation could be established between the depth of sealer penetration and fracture resistance. Fracture resistance of tooth obturated with propoint-bioceramic sealer combination is significantly greater than GP-AH Plus and Resilon-Real seal combination, thereby showing propoint-bioceramic as a promising obturating material.

Cost-effectiveness of sequential daily teriparatide/weekly alendronate compared with alendronate monotherapy for older osteoporotic women with prior vertebral fracture in Japan

SummaryUsing a Markov microsimulation model among hypothetical cohorts of community-dwelling older osteoporotic Japanese women with prior vertebral fracture over a lifetime horizon, we found that daily subcutaneous teriparatide for 2 years followed by weekly oral alendronate for 8 years was not cost-effective compared with alendronate monotherapy for 10 years.PurposeTeriparatide has proven efficacy in reducing osteoporotic fractures, but with substantial cost. We examined the cost-effectiveness of sequential teriparatide/alendronate (i.e., daily subcutaneous teriparatide for 2 years followed by weekly oral alendronate for 8 years) compared with alendronate monotherapy for 10 years among community-dwelling older osteoporotic women with prior clinical or morphometric vertebral fracture in Japan.MethodsUsing a previously validated and updated Markov microsimulation model, we obtained incremental cost-effectiveness ratios (Japanese yen [¥] (or US dollars [$]) per quality-adjusted life year [QALY]) from the perspective of a single payer responsible for both public healthcare and long-term care. We assumed a lifetime horizon with a willingness-to-pay of ¥5million (or $47,500) per QALY in the base case. We modeled the cost of biosimilar teriparatide, which has been available since November 2019 in Japan, assuming the efficacy was the same as that of the brand version.ResultsIn the base case, sequential teriparatide/alendronate was not cost-effective compared with alendronate monotherapy. In deterministic sensitivity analyses, sequential teriparatide/alendronate would become cost-effective with 85%, 50%, and 15% price discounts to teriparatide at ages 70, 75, and 80, respectively, compared to the current biosimilar cost. Otherwise, results were especially sensitive to changes that affected efficacy of teriparatide or alendronate. In probabilistic sensitivity analyses, the probabilities of sequential teriparatide/alendronate being cost-effective were 0%, 1%, and 37% at ages 70, 75, and 80, respectively.ConclusionsAmong high-risk osteoporotic women in Japan, sequential teriparatide/alendronate was not cost-effective compared with alendronate monotherapy, even with the availability of biosimilar teriparatide.