Anti-osteoporotic Therapy Research Articles

Impact of patient education by nurse case managers on decision making for out-of-pocket anti-osteoporotic pharmaceutical therapy: a single-center retrospective study.

Osteoporosis is a common condition that increases the risk of fracture and mortality. In Taiwan, clinical guidelines recommend pharmaceutical therapy for patients with a T-score of ≤ - 2.5; however, Taiwan's National Health Insurance (NHI) only covers these medications for those with a history of fragility fractures. This gap in coverage necessitates a discussion of out-of-pocket treatment options. To address this, we provided an integrated care program with patient education and shared decision-making by nurse case managers specializing in osteoporosis. We evaluated whether education by nurse case managers influences patients with a T-score ≤ - 2.5, who are not covered by the NHI, to choose out-of-pocket pharmaceutical therapy. We retrospectively reviewed medical records of patients who underwent bone density scanning at our hospital between January 2014 and December 2021. We identified 4,462 patients with a T-score of ≤ - 2.5 who were ineligible for NHI-covered anti-osteoporotic therapy and analyzed trends in out-of-pocket medication use. Since the integrated care program began in 2018, we evaluated whether education by nurse case managers between 2018 and 2021 influenced patients' decisions to pay out-of-pocket for therapy. After the implementation of the integrated care program, we identified 2,910 patients with a T-score ≤ -2.5 who were ineligible for NHI-covered anti-osteoporotic therapy. Of these, 640 opted for out-of-pocket treatment, while 2,270 chose conservative care. After a 1:1 propensity score match based on age and sex, logistic regression was used to analyze the impact of nurse case manager education on these decisions. Between 2014 and 2021, 888 of the 4,462 patients chose out-of-pocket pharmaceutical therapy. Before the implementation of the integrated care program and patient education by nurse case managers (2014-2017), 16% of the patients opted to pay out-of-pocket for anti-osteoporotic therapy. After the program was implemented (2018-2021), the rate increased significantly to 22% (P < 0.001). A multivariate logistic regression model showed that a history of osteoarthritis (adjusted odds ratio = 1.576; P = 0.009) and education provided by the nurse case managers (adjusted odds ratio = 5.044; P < 0.001) were significantly associated with choosing out-of-pocket therapy. Education from nurse case managers significantly increased the likelihood of patients choosing out-of-pocket anti-osteoporotic therapy in our hospital, thereby bridging the gap between clinical guidelines and NHI reimbursement criteria.

Anti-Osteoporotic Treatment Reduces Risk of Revision Following Total Shoulder Arthroplasty in Patients with Osteoporosis

Osteoporosis, a prevalent bone density disorder, introduces a complex dynamic in the context of total shoulder arthroplasty (TSA). However, despite the well-established association between osteoporosis and an elevated risk of revision, the existing literature lacks comprehensive insights into the impact of anti-osteoporotic therapy on surgical outcomes in the setting of TSA. Thus, the purpose of this study was to investigate whether anti-osteoporotic therapy correlates with improved revision outcomes following TSA. A retrospective cohort analysis was performed using a national all payer's claims database. Patients who underwent TSA were identified using Current Procedural Terminology (CPT) and International Classification of Diseases (ICD) procedure codes. Patients with a preoperative diagnosis of osteoporosis were included, then stratified into two groups: (1) patients with osteoporosis who underwent anti-osteoporotic therapy within 6 months prior to surgery (Anti-OP cohort) and (2) patients with osteoporosis who never received anti-osteoporotic treatment (No Anti-OP cohort). Primary outcomes included the incidence of 2-year all-cause revision, periprosthetic fracture (PPF), periprosthetic joint infection (PJI), and mechanical loosening. Univariate and multivariable regression analysis was conducted to compare outcomes between the two cohorts. In total, 40,532 osteoporotic patients were included in this study, with 11,577 (28.5%) having undergone anti-osteoporotic treatment. Patients who did not receive anti-osteoporotic treatment had significantly higher odds of 2-year all-cause revision (Odds Ratio [OR]: 1.31; P < 0.001) and mechanical loosening (OR: 1.25; P < 0.001) following TSA when compared to those treated for osteoporosis. This study demonstrates a significant association between anti-osteoporotic therapy and reduced rates of 2-year revision following TSA. Orthopedic surgeons should recognize the heightened risk of early implant failure in the absence of osteoporosis therapy. This underscores the imperative for increased screening initiatives given the high prevalence of undiagnosed or untreated osteoporosis in the TSA population. These results also emphasize the importance of integrating osteoporosis management strategies into the broader context of surgical decision-making, thereby contributing to enhanced patient outcomes and quality of care in shoulder surgery.

Cushing's disease and bone.

Bone impairment associated with Cushing's disease (CD) is a complex disorder, mainly involving deterioration of bone quality and resulting in an increased fracture rate, often despite normal bone mineral density. Bone complications are common in patients with CD at the time of diagnosis but may persist even after successful treatment. There is currently no agreement on the optimal diagnostic methods, thresholds for anti-osteoporotic therapy and its timing in CD. In this review, we summarize the current data on the pathophysiology, diagnostic approach and management of bone complications in CD.

Drug utilization pattern of romosozumab and other osteoporosis treatments in Japan, 2019-2021.

Describe real-world treatment of osteoporosis and romosozumab treatment patterns in Japan. Data for patients initiating romosozumab or other antiosteoporotic medications between March 01, 2018, and May 31, 2022, were extracted from the Medical Data Vision (MDV) and Japan Medical Data Center (JMDC) databases. Patients were categorized into four cohorts: those who newly initiated romosozumab within the first (MDV: n = 4782; JMDC: n = 2578) or second (MDV: n = 3888; JMDC: n = 2446) year after launch and those who initiated teriparatide (TPTD; MDV: n = 14,576; JMDC: n = 8259) or non-TPTD antiosteoporotic medications within the first year of romosozumab launch (MDV: n = 352,142; JMDC: n = 185,785). Mean age, sex, baseline cardiovascular history, comorbidities, and concomitant medications were similar across cohorts. In the MDV database, fracture history was higher in the romosozumab year-1 (59.3%), year-2 (64.1%), and TPTD (65.5%) cohorts versus the non-TPTD cohort (24.4%). Similar rates were identified in the JMDC database: romosozumab year-1 (64.7%), year-2 (66.6%), TPTD (67.5%), and non-TPTD (27.8%). Vertebral fractures were most common in all cohorts. 12-month romosozumab discontinuation varied between the year-1 and year-2 cohorts in MDV (62.4% and 58.8%) and JMDC (57.1% and 52.7%), whereas mean number of injections remained consistent (MDV: 9.7 and 9.8; JMDC: 7.3 and 7.8). Romosozumab persistence was lower in year-1 versus year-2 (MDV: 37.6% and 42.9%; JMDC: 41.2% and 47.3%). Patients initiating romosozumab and TPTD had a high fracture history. Given the dual effects of promoting bone formation and suppressing resorption, improving romosozumab adherence and persistence over time may be important for antiosteoporotic therapy.

Pharmacological prevention of bone loss and fractures following solid organ transplantations: Protocol for a systematic review and network meta-analysis.

Solid organ transplant (SOT) recipients can experience bone loss caused by underlying conditions and the use of immunosuppressants. As a result, SOT recipients are at risk for decreased bone mineral density (BMD) and increased fracture incidences. We propose a network meta-analysis (NMA) that incorporates all available randomized control trial (RCT) data to provide the most comprehensive ranking of anti-osteoporotic interventions according to their ability to decrease fracture incidences and increase BMD in SOT recipients. We will search MEDLINE, EMBASE, Web of Science, CINAHL, CENTRAL and CNKI for relevant RCTs that enrolled adult SOT recipients, assessed anti-osteoporotic therapies, and reported relevant outcomes. Title and full-text screening as well as data extraction will be performed in-duplicate. We will report changes in BMD as weighted or standardized mean differences, and fracture incidences as risk ratios. SUCRA scores will be used to provide rankings of interventions, and quality of evidence will be examined using RoB2 and CINeMA. To our knowledge, this systematic review and NMA will be the most comprehensive quantitative analysis regarding the management of bone loss and fractures in SOT recipients. Our analysis should be able to provide physicians and patients with an up-to-date recommendation for pharmacotherapies in reducing incidences of bone loss and fractures associated with SOT. The findings of the NMA will be disseminated in a peer-reviewed journal.

Surgical management and outcomes following atypical subtrochanteric femoral fractures − results from a matched-pair analysis of the registry for geriatric trauma of the German Trauma Society

Background and objectivesThe outcomes of patients with atypical subtrochanteric fractures (ASFs) remain unclear. Data from a large international geriatric trauma registry were analysed to examine the outcome of patients with ASFs compared to patients with typical osteoporotic subtrochanteric fractures (TSFs).Materials and methodsData from the Registry for Geriatric Trauma of the German Trauma Society (Deutsche Gesellschaft für Unfallchirurgie [DGU]) (ATR-DGU) were analysed. All patients treated surgically for ASFs or TSFs were included in this analysis. Across both fracture types, a paired matching approach was conducted, where statistical twins were formed based on background characteristics sex, age, American Society of Anesthesiologists (ASA) score and walking ability. In-house mortality and mortality rates at the 120-day follow-up, as well as mobility at 7 and 120 days, the reoperation rate, hospital discharge management, the hospital readmission rate at the 120-day follow-up, health-related quality of life, type of surgical treatment and anti-osteoporotic therapy at 7 and 120 days, were assessed as outcome measures using a multivariate logistic regression analysis.ResultsAmongst the 1,800 included patients, 1,781 had TSFs and 19 had ASFs. Logistic regression analysis revealed that patients with ASFs were more often treated with closed intramedullary nailing (RR = 3.59, p < 0.001) and had a higher probability of vitamin D supplementation as osteoporosis therapy at 120 days (RR = 0.88, p < 0.002). Patients with ASFs were also more likely to live at home after surgery (RR = 1.43, p < 0.001), and they also tended to continue living at home more often than patients with TSFs (RR = 1.33, p < 0.001). Accordingly, patients with TSFs had a higher relative risk of losing their self-sufficient living status, as indicated by increased rates of patients living at home preoperatively and being discharged to nursing homes (RR = 0.19, p < 0.001) or other hospitals (RR = 0.00, p < 0.001) postoperatively.ConclusionsSurgical treatment of ASFs was marked by more frequent use of closed intramedullary fracture reduction. Furthermore, patients with ASFs were more likely to be discharged home and died significantly less often in the given timeframe. The rate of perioperative complications, as indicated by nonsignificant reoperation rates, as well as patient walking abilities during the follow-up period, remained unaffected.

Long-term treatment with bisphosphonates in clinical practice: advantages, main problems and risks

Bisphosphonates are the main class of drugs for treatment osteoporosis (OP) and other diseases with increased bone resorption, as bisphosphonates are very effective in reducing risk of fracture. The problem of maintaining the effectiveness and possible loss of effect of bisphosphonates, as well as their safety during long-term use, remains actual Long-them therapy with bisphosphonates and it’s effects has been discussed over the past 20 years, as the risk of osteoporotic fracture may stay hight in patients with presence of irreducible risk factors (continous use of glucocorticoids etc.) despite ongoing antiosteoporotic therapy. Real clinical practice demonstrates very low patient adherence to treatment with bisphosphonates. However, observational studies have showed that treatment with bisphosphonates for more than 10 years without initiating a drug holiday can be effective for patients at high risk of fracture. Moreover, the longer therapy with bisphosphonates is continued and the later the“drug holiday”is initiated, the lower the risks of fractures of the proximal femur and clinical vertebral fractures. However, the duration of continuous bisphosphonate therapy for each patient remains at the decision of the physician and is determined individually in each case, based on the risk-benefit ratio, taking into account the patient’s risk factors for fractures and comorbid diseases.

Osteoporosis is associated with anti-topoisomerase I positivity and glucocorticoids use in patients with systemic sclerosis.

Patients with systemic sclerosis (SSc) are at increased risk for osteoporosis (OP) and associated fragility fractures. This study aimed to identify underlying risk factors for these conditions in patients with SSc. This cross-sectional study was based on a large prospective cohort of patients with SSc using retrospectively collected bone health data. OP was defined as the presence of a T-score below -2.5 at the femoral neck or lumbar spine, a previous major osteoporotic fracture, or the prescription of anti-osteoporotic therapy. A total of 485 patients fulfilling the ACR/EULAR 2013 diagnostic criteria for SSc, followed in the Lille University Hospital, were included in the study. The prevalence of OP was 23%; fragility fractures occurred in 18% of patients. OP was associated with higher age, diffuse cutaneous subset, interstitial lung disease (ILD), anti-topoisomerase I positivity, treatment with glucocorticoids (GC) and DMARDs in univariable analysis. Multivariable analysis indicated that higher age (OR 1.06 [95%CI 1.04-1.08]), anti-topoisomerase I antibody positivity (OR 2.22 [1.18-4.16]) and treatment with GC (OR 4.48 [2.42-8.26]) were significantly and independently associated with OP. Our study shows that OP risk in patients with SSc is determined by age, disease-related factors such as diffuse cutaneous subset, ILD and anti-topoisomerase I antibody positivity, but also treatment with GC independently of other factors.

Ukrainian Consensus on Diagnosis and Management of Vitamin D Deficiency in Adults.

Vitamin D deficiency (VDD) is a global problem, however, there were no Ukrainian guidelines devoted to its screening, prevention, and treatment, which became the reason for the Consensus creation. This article aimed to present the Consensus of Ukrainian experts devoted to VDD management. Following the creation of the multidisciplinary Consensus group, consent on the formation process, drafting and fine-tuning of key recommendations, and two rounds of voting, 14 final recommendations were successfully voted upon. Despite a recent decrease in VDD prevalence in Ukraine, we recommend raising awareness regarding VDD's importance and improving the strategies for its decline. We recommend screening the serum 25-hydroxyvitamin D (25(OH)D) level in risk groups while maintaining a target concentration of 75-125 nmol/L (30-50 ng/mL). We recommend prophylactic cholecalciferol supplementation (800-2000 IU/d for youthful healthy subjects, and 3000-5000 IU/d for subjects from the risk groups). For a VDD treatment, we recommend a short-term administration of increased doses of cholecalciferol (4000-10,000 IU/d) with 25(OH)D levels monitored after 4-12 weeks of treatment, followed by the use of maintenance doses. Additionally, we recommend assessing serum 25(OH)D levels before antiosteoporotic treatment and providing vitamin D and calcium supplementation throughout the full course of the antiosteoporotic therapy.

Potential application of anti-osteoporotic therapy to relieve sarcopenia in the elderly

Sarcopenia is a progressive and systemic skeletal muscle disorder associated with aging that usually occurs with age in the elderly. Sarcopenia currently lacks effective pharmacological treatment modalities. Multiple pharmacological intervention modalities are available for osteoporosis, a comprehensive disease characterized by decreased systemic bone mass, degradation of bone microarchitecture, and increased bone fragility. Several recent studies have shown an extremely strong correlation between sarcopenia and osteoporosis, leading to the concept of “osteosarcopenia”. Therefore, it is possible to alleviate sarcopenia simultaneously by improving osteoporosis.

Peptide-modified PAMAM-based bone-targeting RNA delivery system

BackgroundOsteoporosis, among other bone diseases, has become a prevalent cause of decreased quality of life in older and postmenopausal women. Traditional anti-osteoporotic therapies, though widely prescribed, are limited by a lack of cell- or tissue-specific targeting ability and effectiveness without side effects. Gene therapy is rapidly replacing traditional therapeutics, primarily because of its specific targeting ability and efficiency. Among viral- and non-viral-based gene therapies, the latter is often preferred over the former due to lower cytotoxicity, immunogenicity, and ease of modification with different molecules to improve efficiency and extend gene expression. We designed and synthesized a multifunctional bone-targeting ribonucleic acid (RNA) delivery system based on polyamidoamine (PAMAM). PAMAM was modified with the serine-aspartate-serine-serine-aspartate (SDSSD) peptide to deliver antagomir 138-5p to osteoblasts (MC3T3-E1 cell line) in vitro and in vivo using the ovariectomized (OVX) mouse model.ResultsThe results showed that this system was less cytotoxic than polyethylenimine (PEI) and could bind to RNA favorably while maintaining gene delivery ability in vitro. In vivo data showed that the distal tibia and femur of the mice in the PAMAM-SDSSD (PS) + RNA group had improved bone mineral density (BMD), bone mineral content (BMC), and bone volume compared to those in the PS + Negative Control (NC) or OVX groups. Moreover, the femurs of the PS + RNA group mice demonstrated a higher breaking point, stress, stiffness, and elasticity than those of the PS + NC or OVX mice, suggesting improved femur strength in the OVX mice treated with RNA delivered through SDSSD-modified PAMAM.ConclusionThis study shows that SDSSD modification of PAMAM not only improves gene delivery capacity but also enhances the cell targeting efficiency of nanoparticles towards osteoblasts. The successful delivery of antagomir 138-5p to osteoblasts demonstrates cell-specificity and gene delivery to alleviate osteoporotic symptoms.

Characterization and effectiveness of a Fracture Liaison Services program in Colombia

PurposeFracture Liaison Services programs reduce mortality and the risk of refracture and increase treatment and adherence rates. Greater coverage is an important priority for the future. The aim was to determine the characteristics of patients over 50 years old who suffered fractures and the effectiveness of a Fracture Liaison Services program in a health care institution in Colombia.MethodsThis was a retrospective follow-up study of a cohort of patients with vertebral and nonvertebral fractures managed in a Fracture Liaison Services program. Sociodemographic, clinical and pharmacological variables were identified. Key performance indicators were used to evaluate the effectiveness of the program. Descriptive and bivariate analysis was performed.ResultsA total of 438 patients were analyzed. The average age was 77.5 years, and 78.5% were women. Hip and vertebral fractures were the most common (25.3% and 24.9%, respectively). Vertebral fractures prevailed in men (33.0% vs 22.7%; p = 0.041) and those of the radius/ulna in women (20.3% vs 10.6%; p = 0.031). A total of 29.7% had experienced a previous fracture, and 16.7% had received antiosteoporosis drugs. A total of 63.5% of the cases were managed surgically. At discharge, 58.8% received prescriptions for calcium/vitamin D, and 50.7% with prescriptions of antiosteoporotic therapy, especially teriparatide (21.2%) and denosumab (16.4%), without significant differences by sex. However, in women with hip fractures, anti-osteoporotic management prevailed (83.7% vs 64.0; p = 0.032). The effectiveness of the overall program per year was 74.6%. On follow-up, only 9.1% of patients had experienced a new fall, and of those 3.7% presented a new fracture. A total of 4.3% died during follow-up.ConclusionsGood adherence to the recommendations of the country's clinical practice guidelines was found, and overall, the effectiveness of the program was very satisfactory, with a low incidence of new fractures during follow-up.SummaryFracture Liaison Services programs reduce mortality and the risk of refracture. A retrospective follow-up study of a cohort of patients with vertebral and nonvertebral fractures managed in a Fracture Liaison Services, showed that the effectiveness was 73.6%. On follow-up, 9.1% of patients had experienced a new fall, and of those 3.7% presented a new fracture.

Association between resolved hepatitis B virus infection and femoral and spinal bone mineral density in American adults: a cross-sectional study.

Hepatitis B virus (HBV) infection is a global health concern that can potentially affect bone health. However, the specific association between resolved HBV infection and bone mineral density (BMD) remains unclear. This cross-sectional study aimed to investigate the potential association between resolved HBV infection and femoral and spinal BMD in adults in the United States. This cross-sectional study included participants aged 20-79 years with negative HBV surface antigen (HBsAg) from the 2005-2010, 2013-2014, and 2017-2018 cycles of the National Health and Nutrition Examination Survey. Resolved HBV infection was defined as negative HBsAg with positive HBV core antibody. BMD was measured using dual-energy X-ray absorptiometry. Propensity score matching (PSM) was performed to balance baseline characteristics. A total of 10,333 eligible participants were identified and matched, of whom 737 (7.1%) had resolved HBV infection. Men with resolved HBV infection had significantly lower femoral and spinal BMD compared to those with no HBV infection, both before and after PSM. In the matched population, resolved HBV infection in men was negatively associated with femoral BMD (β= -0.024, 95% CI: -0.047 to -0.002, p = 0.0332) and spinal BMD (β= -0.025, 95% CI: -0.048 to -0.002, p = 0.0339). Postmenopausal women exhibited similar trends to men, while premenopausal women showed a tendency towards higher BMD, although statistical significance was not consistently achieved. Subgroup and sensitivity analyses supported the robustness of the findings. The study suggests a negative association between resolved HBV infection and femoral and spinal BMD in adult men in the United States. It highlights the importance of routine bone density assessments and the consideration of anti-osteoporotic therapy, if necessary, in individuals with resolved HBV infection.

Low disease activity state associated with fewer incident vertebral fractures in Mestizo women with systemic lupus erythematosus.

Low disease activity state (LDAS) has been linked to a significant reduction in flares and damage accrual in patients with systemic lupus erythematosus (SLE); however, the effect of LDAS on the risk of vertebral fractures (VFs) in subjects with SLE is unknown, considering that low bone mineral density (BMD) and VF are frequent in SLE. to evaluate whether achieving LDAS ≥50% of the observation time prevents new VF and BMD changes in Mestizo women. We carried out a longitudinal, observational, and retrospective study. Mestizo women with SLE were included for a median of an 8-year follow-up. LDAS was described as Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score ≤4, prednisone ≤7.5mg/day, and stable immunosuppressive therapies. BMD measurements and lateral thoracic and lumbar radiographs for a semiquantitative analysis for VF were assessed at baseline and during the follow-up. Uni- and multivariable interval-censored survival regression models were carried out. We included 110 patients: 35 (31.8%) had new VF. A total of 56 patients (50.1%) achieved LDAS ≥50% of the time during the follow-up and achieved a significantly lesser risk of incident VF (HR = 0.16; 95% CI, 0.06-0.49). After adjusting by age, BMI, menopause, prevalent VF, baseline BMD, cumulative glucocorticoid use, and anti-osteoporotic therapy, LDAS-50 was significantly related to a decrease in the risk of a new VF (HR = 0.39; 95% CI, 0.16-0.98). There was no association between LDAS and BMD measurement changes. When only patients on LDAS but not in remission (n = 43) were evaluated for the risk of incident VF, both uni- and multivariate analyses were significant (HR = 0.12; 95 CI, 0.04-47; p = 0.001, and HR = 0.26; 95% CI, 0.7-0.88; p = 0.03). LDAS ≥50% of the time was significantly associated with a diminished risk of new VF in Mestizo women with SLE, even in patients not in remission. However, LDAS did not help modify BMD changes over time.

Impact of Anxiety During Hospitalization on the Clinical Outcome of Patients With Osteoporotic Thoracolumbar Vertebral Fracture.

Multicenter prospective cohort study. Anxiety in combination with osteoporotic vertebral compression fractures (OVCFs) of the spine remains understudied. The purpose of this study was to analyze whether anxiety has an impact on the short-term functional outcome of patients with an OVCF. Furthermore, a direct impact of the fracture on the patient's anxiety during hospitalization should be recognized. All inpatients with an OVCF of the thoracolumbar spine from 2017 to 2020 were included. Trauma mechanism, analgetic medication, anti-osteoporotic therapy, timed-up-and-go test (TuG), mobility, Barthel index, Oswestry-Disability Index (ODI) and EQ5D-5L were documented.For statistical analysis, the U test, chi-square independence test, Spearman correlation, General Linear Model for repeated measures, Bonferroni analysis and Wilcoxon test were used. The item anxiety/depression of the EQ5D-5L was analyzed to describe the patients' anxiousness. Data from 518 patients from 17 different hospitals were evaluated. Fracture severity showed a significant correlation (r = .087, P = .0496) with anxiety. During the hospital stay, pain medication (P < .001), anti-osteoporotic medication (P < .001), and initiation of surgical therapy (P < .001) were associated with less anxiety. The anxiety of a patient at discharge was negatively related to the functional outcomes at the individual follow-up: TuG (P < .001), Barthel index (P < .001), ODI (P < .001) and EQ5D-5L (P < .001). Higher anxiety is associated with lower functional outcome after OVCF. The item anxiety/depression of the EQ5D-5L provides an easily accessible, quick and simple tool that can be used to screen for poor outcomes and may also offer the opportunity for a specific anxiety intervention.

Influence of non-osteoporotic treatments in patients on active anti-osteoporotic therapy: evidence from the OSTEOMED registry

PurposeTo evaluate the effect of different non-osteoporotic drugs on the increase or decrease in the risk of incident fragility fractures (vertebral, humerus or hip) in a cohort of patients diagnosed with osteoporosis on active anti-osteoporotic therapy.MethodsFor this retrospective longitudinal study, baseline and follow-up data on prescribed non-osteoporotic treatments and the occurrence of vertebral, humerus or hip fractures in 993 patients from the OSTEOMED registry were analyzed using logistic regression models. The drugs evaluated with a possible beneficial effect were thiazides and statins, while the drugs evaluated with a possible harmful effect were antiandrogens, aromatase inhibitors, proton pump inhibitors, selective serotonin reuptake inhibitors, benzodiazepines, GnRH agonists, thyroid hormones, and oral and inhaled corticosteroids.ResultsLogistic regression analyses indicated that no treatment significantly improved fracture risk, with the only treatments that significantly worsened fracture risk being letrozole (OR = 0.18, p-value = 0.03) and oral corticosteroids at doses ≤ 5 mg/day (OR = 0.16, p-value = 0.03) and > 5 mg/day (OR = 0.27, p-value = 0.04).ConclusionThe potential beneficial or detrimental effects of the different drugs evaluated on fracture risk are masked by treatment with anabolic or antiresorptive drugs that have a more potent action on bone metabolism, with two exceptions: letrozole and oral corticosteroids. These findings may have important clinical implications, as patients receiving these treatments are not fully protected by bisphosphonates, which may imply the need for more potent anti-osteoporotic drugs such as denosumab or teriparatide.

Diagnosis, prevention and treatment of vitamin D deficiency in adults: Ukrainian experts consensus statement

Background. Vitamin D deficiency (VDD) is widespread in the world; its proportion varies considerably in different populations and depends on many causes. Up to now, there were no National recommendations for the diagnosis, prevention, and treatment of VDD in adults in Ukraine. Their creation became the purpose of this work. Methodology. Consensus was created using the Delphi method, voting was conducted using the SurveyMonkey® platform. After approval of the composition of the Consensus Group, agreement on the order of formation and structure of the Consensus, creation and correction of the main statements, and two voting rounds, the main Consensus statements were formed and were successfully voted on. The 15 authors of the article are 15 experts who participated in the voting. The final 14 Consensus statements are presented in this article. Each statement is preceded by a justification based on high-quality evidence available in the current literature. Results. Despite the reduction of VDD in the Ukrainian population in recent years, experts have recommen­ded increasing the awareness of the medical community and the Ukrainian population about the problem and ways to overcome it, with a screening of the total serum level of 25-hydroxyvitamin D (25(OH)D) in subjects from the groups of risk to achieve the target concentration of 30–50 ng/ml (75–125 nmol/l). To ensure it, we recommend the individual selection of a prophylactic dose of vitamin D (800–2000 IU/d for young healthy persons and 3000–5000 IU/d for patients with diseases and conditions that affect the metabolism of vitamin D). For the treatment of VDD, we recommend short-term intake of higher doses (4000–10,000 IU/d) of vitamin D with control of the 25(OH)D level after 4–12 weeks of treatment and subsequent use of maintenance doses. Also, we re­commend the determination of serum 25(OH)D level before the initiation of antiosteoporotic therapy in patients with osteoporosis and its complications to prevent its ineffectiveness and increase the safety profile.

Severe osteoporosis in a young man with bilateral Cushing’s syndrome: a case report

BackgroundThe diagnosis of Cushing’s syndrome is challenging; however, through the clinical picture and the search for secondary causes of osteoporosis, it was possible to reach the diagnosis of the case reported. There was an independent, symptomatic ACTH hypercortisolism manifested by typical phenotypic changes, severe secondary osteoporosis and arterial hypertension in a young patient.Case presentationA 20-year-old Brazilian man with low back pain for 8 months. Radiographs showed fragility fractures in the thoracolumbar spine, and bone densitometry showed osteoporosis, especially when evaluating the Z Score (− 5.6 in the lumbar spine). On physical examination, there were wide violaceous streaks on the upper limbs and abdomen, plethora and fat increase in the temporal facial region, hump, ecchymosis on limbs, hypotrophy of arms and thighs, central obesity and kyphoscoliosis. His blood pressure was 150 × 90 mmHg. Cortisol after 1 mg of dexamethasone (24.1 µg/dL) and after Liddle 1 (28 µg/dL) were not suppressed, despite normal cortisoluria. Tomography showed bilateral adrenal nodules with more severe characteristics. Unfortunately, through the catheterization of adrenal veins, it was not possible to differentiate the nodules due to the achievement of cortisol levels that exceeded the upper limit of the dilution method. Among the hypotheses for the differential diagnosis of bilateral adrenal hyperplasia are primary bilateral macronodular adrenal hyperplasia, McCune–Albright syndrome and isolated bilateral primary pigmented nodular hyperplasia or associated with Carney’s complex. In this case, primary pigmented nodular hyperplasia or carcinoma became important etiological hypotheses when comparing the epidemiology in a young man and the clinical-laboratory-imaging findings of the differential diagnoses. After 6 months of drug inhibition of steroidogenesis, blood pressure control and anti-osteoporotic therapy, the levels and deleterious metabolic effects of hypercortisolism, which could also impair adrenalectomy in the short and long term, were reduced. Left adrenalectomy was chosen, given the possibility of malignancy in a young patient and to avoid unnecessary definitive surgical adrenal insufficiency if the adrenalectomy was bilateral. Anatomopathology of the left gland revealed expansion of the zona fasciculate with multiple nonencapsulated nodules.ConclusionThe early identification of Cushing’s syndrome, with measures based on the assessment of risks and benefits, remains the best way to prevent its progression and reduce the morbidity of the condition. Despite the unavailability of genetic analysis for a precise etiological definition, it is possible to take efficient measures to avoid future damage.

Effects of anti-osteoporosis therapy on the risk of secondary fractures and surgical complications following surgical fixation of proximal humerus fracture in older people.

age-related fragility fractures cause significant burden of disease. Within an ageing society, fracture and complication prevention will be essential to balance health expenditure growth. to assess the effect of anti-osteoporotic therapy on surgical complications and secondary fractures after treatment of fragility fractures. retrospective health insurance data from January 2008 to December 2019 of patients ≥65years with proximal humeral fracture (PHF) treated using locked plate fixation (LPF) or reverse total shoulder arthroplasty were analysed. Cumulative incidences were calculated by Aalen-Johansen estimates. The influence of osteoporosis and pharmaceutical therapy on secondary fractures and surgical complications were analysed using multivariable Fine and Gray Cox regression models. a total of 43,310 patients (median age 79years, 84.4% female) with a median follow-up of 40.9months were included. Five years after PHF, 33.4% of the patients were newly diagnosed with osteoporosis and only 19.8% received anti-osteoporotic therapy. A total of 20.6% (20.1-21.1%) of the patients had at least one secondary fracture with a significant reduction of secondary fracture risk by anti-osteoporotic therapy (P < 0.001). An increased risk for surgical complications (hazard ratio: 1.35, 95% confidence interval: 1.25-1.47, P < 0.001) after LPF could be reversed by anti-osteoporotic therapy. While anti-osteoporotic therapy was more often used in female patients (35.3 vs 19.1%), male patients showed significantly stronger effects reducing the secondary fracture and surgical complication risk. a significant number of secondary fractures and surgical complications could be prevented by consequent osteoporosis diagnosis and treatment particularly in male patients. Health-politics and legislation must enforce guideline-based anti-osteoporotic therapy to mitigate burden of disease.

Discrepancies in type of first major osteoporotic fracture and anti-osteoporotic therapy in elderly people with type 2 diabetes mellitus: A retrospective Danish cohort study.

Subjects with diabetes mellitus have an increased risk of fractures. We aimed to identify discrepancies in the first type of major osteoporotic fracture (MOF) and anti-osteoporotic therapy between subjects with type 2 diabetes (T2D) and subjects without diabetes. Methods and research design. We conducted a retrospective national cohort study by access to all discharge diagnoses (ICD-10 system) and redeemed drug prescriptions (ATC classification system). We included all subjects alive and Danish citizens in 2010 and identified subjects with T2D diagnosed after the age of 50 between 1998 and 2018. Only subjects with a MOF after the index date were included in the main analysis. The type of MOF was identified by diagnosis codes and categorized into Humerus, Forearm, Spine, and Hip. Multinomial logistic regression modeling was used to assess the predicted probability changes in MOF type between T2D and control subjects. Data on first anti-osteoporotic therapy after the MOF was assessed by redeemed drug prescriptions. Mortality and time to therapy after the MOF were evaluated by cox proportional hazards. We included 26,588 subjects with T2D and 97,982 subjects without diabetes. The mean age was age 69.33 (±10.34) for T2D and 69.85 (±10.19) for control subjects. The cohort was primarily females (67%). Subjects with T2D had a higher probability of hip (3.98% [95% CI 3.29; 4.67]) and humerus (2.82% [95% CI 2.17; 3.46]) fractures as the first MOF compared to control subjects. However, the probability of forearm fractures as the first MOF was 6.77% (95% CI 6.08; 7.46) lower among subjects with T2D. The multiple adjusted hazard ratio for anti-osteoporotic treatment after the first MOF was 0.80 (95% CI 0.77; 0.88) for T2D compared to controls among treatment-naïve subjects. Forearm fractures were the most frequent type of MOF and were more prevalent in control subjects. Subjects with T2D had a significantly higher probability of hip and humerus fractures as the first MOF but had a 20% lower chance of anti-osteoporotic treatment afterwards.