Risk Of Nonvertebral Fractures Research Articles

A practical approach for anabolic treatment of bone fragility with romosozumab.

Romosozumab, a fully humanized anti-sclerostin-antibody, is a bone-builder stimulating osteoblasts and inhibiting osteoclast by activation of the canonical Wnt-beta catenin signaling. This unique mechanism of action has the potential to address unmet needs in osteoporosis management. The multifaceted practical clinical issues related to romosozumab are discussed, especially focusing on the rationale of employing a sclerostin inhibitor to target bone fragility as first line or second line treatment in post-menopausal osteoporosis and in males at increased risk of fractures. Four randomized clinical trials with several post-hoc analyses and more than ten observational studies have consistently demonstrated that romosozumab is effective in rapidly increasing bone mineral density (BMD) and decreasing risk of vertebral, non-vertebral and hip fractures in post-menopausal women at very-high risk of fractures. In male osteoporosis, only data on BMD are available. Noteworthy, romosozumab was shown to be more effective and rapid than teriparatide in improving BMD, bone structure and strength at the hip, especially in women already treated with anti-resorptive drugs. Interestingly, even if romosozumab displays best results in treatment-naïve patients, its favourable effects on BMD were observed even in women previously treated with teriparatide or denosumab, although to a lesser extent. Based on the available evidence, romosozumab could be proposed as ideal drug in several clinical settings, such as non-fractured post-menopausal women at very-high risk of fractures, patients with recent hip fracture, patients non responder to bisphosphonates and short-term denosumab therapy.

Effects of Abaloparatide on Bone Mineral Density in Proximal Femoral Regions Corresponding to Arthroplasty Gruen Zones: A Study of Postmenopausal Women with Osteoporosis.

Low hip bone mineral density (BMD) in patients who undergo total hip arthroplasty (THA) increases the risk of periprosthetic fractures, implant instability, and other complications. Recently, emphasis has been placed on bone health optimization: treating low BMD prior to a planned orthopaedic implant procedure in an effort to normalize BMD and reduce the potential risk of future complications. Abaloparatide is a U.S. Food and Drug Administration-approved osteoanabolic agent for men and postmenopausal women with osteoporosis and a candidate drug for bone health optimization that, in addition to benefits at the spine, increases hip BMD and reduces nonvertebral fracture risk. We hypothesized that abaloparatide would improve BMD in proximal femoral regions surrounding a virtual THA stem. This post hoc analysis obtained dual x-ray absorptiometry (DXA) hip scans from 500 randomly selected postmenopausal women with osteoporosis from the Phase-3 Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE, NCT01343004) study after 0, 6, and 18 months of abaloparatide (250 patients) or placebo (250 patients). Hip DXA scans underwent 3-dimensional (3D) modeling via 3D-Shaper, followed by virtual resection of the proximal femur and simulated placement of a tapered, flat-wedge hip stem that guided delineation of the Gruen zones that were fully (zones 1 and 7) or largely (zones 2 and 6) captured in the scanning region. Integral, cortical, and trabecular volumetric BMD, cortical thickness, and cortical surface BMD (the product of cortical volumetric BMD and cortical thickness) were determined for each zone. Compared with placebo, the abaloparatide group showed greater increases in integral volumetric BMD in all zones at months 6 and 18; cortical surface BMD in zones 1, 6, and 7 at month 6; cortical thickness, cortical volumetric BMD, and cortical surface BMD in all zones at month 18; and trabecular volumetric BMD in zones 1 and 7 at months 6 and 18. Abaloparatide increases BMD in proximal femoral regions that interact with and support femoral stems, suggesting that abaloparatide may have value for preoperative or potentially perioperative bone health optimization in patients with osteoporosis undergoing THA. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Links among Obesity, Type 2 Diabetes Mellitus, and Osteoporosis: Bone as a Target.

Obesity, type 2 diabetes mellitus (T2DM) and osteoporosis are serious diseases with an ever-increasing incidence that quite often coexist, especially in the elderly. Individuals with obesity and T2DM have impaired bone quality and an elevated risk of fragility fractures, despite higher and/or unchanged bone mineral density (BMD). The effect of obesity on fracture risk is site-specific, with reduced risk for several fractures (e.g., hip, pelvis, and wrist) and increased risk for others (e.g., humerus, ankle, upper leg, elbow, vertebrae, and rib). Patients with T2DM have a greater risk of hip, upper leg, foot, humerus, and total fractures. A chronic pro-inflammatory state, increased risk of falls, secondary complications, and pharmacotherapy can contribute to the pathophysiology of aforementioned fractures. Bisphosphonates and denosumab significantly reduced the risk of vertebral fractures in patients with both obesity and T2DM. Teriparatide significantly lowered non-vertebral fracture risk in T2DM subjects. It is important to recognize elevated fracture risk and osteoporosis in obese and T2DM patients, as they are currently considered low risk and tend to be underdiagnosed and undertreated. The implementation of better diagnostic tools, including trabecular bone score, lumbar spine BMD/body mass index (BMI) ratio, and microRNAs to predict bone fragility, could improve fracture prevention in this patient group.

Efficacy and Safety of Generic Alendronate for Osteoporosis Treatment.

While osteoporosis increases the risk of fragility fractures, bisphosphonate has been proven to increase bone strength and reduce the risk of vertebral and non-vertebral fractures. In addition to its efficacy, substituting the brand with generic medication is a strategy to optimize healthcare expenditures. This study aimed to evaluate the efficacy of generic alendronate treatment and assess potential adverse events in patients with osteoporosis. A retrospective review was conducted on 120 patients who met the indications for osteoporosis treatment, received weekly generic alendronate (70 mg) for >1 year, and underwent evaluation through standard axial dual-energy X-ray absorptiometry (DXA). The outcomes of this study were the percent change in bone mineral density (BMD) at the lumbar spine, femoral neck, and total hip after one year of treatment. The major adverse events occurring during medication that led to the discontinuation of drug administration were documented. Most patients were female (96.7%) with an average age of 69.0 ± 9.3 years. The percent change in BMD increased at all sites after one year of generic alendronate treatment (lumbar spine: 5.6 ± 13.7, p-value <0.001; femoral neck: 2.3 ± 8.3, p-value = 0.023; total hip: 2.1 ± 6.2, p-value = 0.003), with over 85% of patients experiencing increased or stable BMD. Three patients discontinued the medication due to adverse effects: two had dyspepsia, and one had persistent myalgia. Generic alendronate may be considered an effective antiresorptive agent for osteoporosis treatment with a low incidence of adverse effects.

Association of secondhand smoke with fracture risk in community-dwelling nonsmoking adults in Korea.

Although the detrimental effects of active smoking on bone health have been widely recognized, the impact of secondhand smoke exposure on fracture risk in non-smokers remains less understood. A total of 4843 nonsmokers aged 40-69yr, who participated in the Korean Genome and Epidemiology Study from 2001 to 2018, were analyzed. The participants were categorized into two groups based on their exposure status to secondhand smoke: currently exposed and unexposed. The exposure group was subsequently divided into two subgroups based on the median weekly exposure time (high vs low). The incidence of new fractures was determined using self-reported questionnaires. The identified fractures were categorized according to the fracture site: overall, vertebral, hip, non-vertebral, and non-vertebral non-hip fractures. The mean age of the participants was 52.4yr (84.1% women). Exposure to secondhand smoke was associated with an increased risk of fracture (adjusted hazard ratio [aHR]: 1.27, P =0.028) after adjusting for multiple covariates including age, sex, BMI, household income, bone density of mid-shaft tibia, C-reactive protein, alcohol consumption, and fracture history. Secondhand smoke remained as a significant risk factor for fracture, independent of the major osteoporotic fracture probabilities estimated using a fracture risk assessment tool (aHR: 1.24, P =0.038). The high exposure group had higher risk of fracture than that of the unexposed group (aHR: 1.33, P =0.025), whereas the fracture risk did not differ significantly between low exposure and unexposed groups (aHR: 1.18, P =0.253), suggesting a potential dose-response relationship. Secondhand smoke showed robust association with increased risk of non-vertebral (aHR: 1.37, P =0.008) or non-vertebral non-hip fractures (aHR: 1.36, P =0.013), while its association with vertebral fracture was attenuated (aHR: 1.03, P =0.908). Secondhand smoke was associated with an elevated risk of fracture in nonsmokers, independent of clinical risk factors.

Antiosteoporosis therapy after discontinuation of menopausal hormone therapy: a systematic review.

Menopausal hormone therapy (MHT) has consistently shown a bone protective effect by reducing the risk of vertebral, non-vertebral, and hip fractures in postmenopausal women regardless of baseline fracture risk. However, the optimal sequential treatment after MHT discontinuation has not been determined. This systematic review aimed to obtain the best evidence regarding the effect of antiresorptive or osteoanabolic treatment on bone mineral density (BMD) and/or fracture risk following MHT. A comprehensive search was conducted in the PubMed, Scopus, and Cochrane databases up to October 31, 2023. Randomized-controlled trials (RCTs) and observational studies conducted in postmenopausal women were included. After the exclusion of duplicates, 717 studies were identified. Two were eligible for qualitative analysis, one RCT and one retrospective cohort study. The RCT showed that alendronate 10mg/day for 12months further increased lumbar spine (LS) BMD by 2.3% following MHT and maintained femoral neck (FN) BMD in postmenopausal women (n = 144). It also decreased bone anabolic and resorption markers by 47 and 36%, respectively. In the retrospective study (n = 34), raloxifene 60mg/day increased both LS and FN BMD at 12months by 3 and 2.9%, respectively. No fractures were reported. Antiresorptive therapy with either a bisphosphonate (i.e., alendronate) or raloxifene could be considered a sequential antiosteoporosis therapy after MHT withdrawal since they have been shown in studies to further increase BMD. However, no safe conclusions can be drawn from the existing literature.

OP129 A Cost-Utility Analysis Of Denosumab (Prolia®) For Treating Osteoporosis In Postmenopausal Women: A Swiss Healthcare Payer Perspective

IntroductionOsteoporosis is characterized by decreased bone mass and density, increasing skeletal fragility, and the risk of fragility fracture. Fragility fractures are associated with a high economic burden. Denosumab (Prolia®) is a pharmacological therapy used to treat osteoporosis and reduce the risk of fragility fracture. This study aimed to assess the cost effectiveness of denosumab, compared with other pharmacological therapies (oral bisphosphonates, intravenous [IV] ibandronate, zoledronate, raloxifene, and bazedoxifene) and no treatment, for treating postmenopausal women with osteoporosis.MethodsA discrete event simulation model was developed using a lifetime time horizon. A Swiss healthcare payer perspective was adopted. Time-to-fracture distributions were derived from Swiss-specific Fracture Risk Assessment Tool (FRAX®) probabilities. Reductions in the risk of vertebral and nonvertebral fractures due to treatment were informed by a Bayesian network meta-analysis. Cost-effectiveness frontier analysis was utilized. Pairwise incremental cost-effectiveness ratios (ICERs) between denosumab and each comparator were also estimated. Sensitivity analyses were conducted to identify key drivers and explore the overall certainty of findings.ResultsAt a hypothetical willingness-to-pay (WTP) threshold of CHF100,000 (EUR101,630), IV ibandronate was the most cost-effective therapy in women aged 60 years who had a very high risk of fracture, and in women aged 70 or 80 years of any risk level. In women aged 60 years with a lower risk level, zoledronate was the most cost-effective option. Nevertheless, ICERs from pairwise comparisons between denosumab and some comparators (no treatment, bazedoxifene, raloxifene, and/or zoledronate depending on the cohort’s age and risk profile) were below the hypothetical WTP threshold. Higher intervention costs, smaller reductions in the risk of hip fracture, and shorter duration of residual benefit associated with denosumab contributed to the high ICER values seen in pairwise comparisons with oral bisphosphonates (as a class) and IV ibandronate.ConclusionsThe present evaluation supported the cost effectiveness of denosumab against some, but not all, comparators. Nevertheless, these results should be interpreted cautiously in light of uncertainty in the true effect of treatments on fracture risk.

Role of Calcitonin and Strontium Ranelate in Osteoporosis.

Both Strontium Ranelate (SR) and Calcitonin (CT) can be used to treat osteoporosis. Calcitonin was actually one of the very initial medicines used to treat osteoporosis, especially in postmenopausal cases. However, the fracture prevention effect of Calcitonin is only proven to be in vertebrae and that too with nasal route only. When comparing Calcitonin with other conventional medications in treating osteoporosis, Calcitonin has got no additional advantages. Strontium Ranelate has got double effect, i.e., less bone resorption and more bone formation. Therefore, it can lead to an increase in bone mass significantly. Strontium Ranelate has been proven to decrease the risk of non-vertebral fractures as well as vertebral fractures. Both Calcitonin and Strontium Ranelate are used only as a second-line therapy for the treatment of osteoporosis and not as first-line therapy, mainly because of their safety concern and also because they do not provide any advantages compared to other therapy for the treatment of osteoporosis.

Risk of fracture in women with glucocorticoid requiring diseases is independent from glucocorticoid use: An analysis on a nation-wide database

ObjectiveGlucocorticoid-induced osteoporosis (GIOP) is a common cause of secondary osteoporosis. However, glucocorticoid requiring diseases pose a risk themselves for fracture. The aim of the present study was to determine the risk of fracture associated with variety of glucocorticoid requiring diseases independently from glucocorticoid use and other risk factors for osteoporosis. MethodsWe conducted a retrospective cross-sectional analysis of a nation-wide cohort (DeFRACalc79 database). We used multivariable regression analysis adjusting for several risk factors for fracture and glucocorticoid intake to estimate the independent role of glucocorticoid requiring illnesses on fracture risk. ResultsWe found that patients with rheumatoid arthritis, connective tissue diseases, chronic obstructive pulmonary disease (COPD) and neurological diseases were at greater risk of vertebral or hip fracture (crude ORs 1.31, 1.20, 1.92 and 2.97 respectively). After adjusting for potential confounders COPD and neurological diseases remained significantly associated with an increased risk of vertebral or hip fractures (aORs 1.33, 95 % CI 1.18–1.49 and 2.43, 95 % CI 2.17–2.74). Rheumatoid arthritis, COPD, IBD and neurological diseases also significantly increased the risk of non-vertebral, non-hip fractures (aORs 1.23, 1.42, 1.52 and 1.94 respectively). ConclusionSome glucocorticoid requiring diseases were independently associated with an increased risk of fractures. COPD and neurological diseases with both vertebral and non-vertebral fracture risk while RA and IBD were independently associated only with non-vertebral, non-hip fractures.

Antiresorptive Versus Anabolic Therapy in Managing Osteoporosis in People with Type 1 and Type 2 Diabetes.

Diabetes is characterized by hyperglycemia, but the two main types, type 1 diabetes (T1D) and type 2 diabetes (T2D), have distinct pathophysiology and epidemiological profiles. Individuals with T1D and T2D have an increased risk of fractures, particularly of the hip, upper arm, ankle, and nonvertebral sites. The risk of fractures is higher in T1D compared to T2D. The diagnosis of osteoporosis in individuals with T1D and T2D follows similar criteria as in the general population, but treatment thresholds may differ. Antiresorptive therapies, the first-line treatment for osteoporosis, are effective in individuals with T2D. Observational studies and post hoc analyses of previous trials have indicated that antiresorptive drugs, such as bisphosphonates and selective estrogen receptor modulators, are equally effective in reducing fracture risk and increasing bone mineral density (BMD) in individuals with and without T2D. Denosumab has shown similar effects on vertebral fracture risk but increases the risk of nonvertebral fractures. Considering the low bone turnover observed in T1D and T2D, anabolic therapies, which promote bone formation and resorption, have emerged as a potential treatment option for bone fragility in this population. Data from observational studies and post hoc analyses of previous trials also showed similar results in increasing BMD and reducing the risk of fractures in people with or without T2D. However, no evidence suggests that anabolic therapy has greater efficacy than antiresorptive drugs. In conclusion, there is an increased risk of fractures in T1D and T2D. Reductions in BMD cannot solely explain the relationship between T1D and T2D and fractures. Bone microarchitecture and other factors play a role. Antiresorptive and anabolic therapies have shown efficacy in reducing fracture risk in individuals with T2D, but the evidence is more robust for antiresorptive drugs. Evidence in T1D is scant. Further research is needed to fully understand the underlying mechanisms and optimize management strategies for bone fragility in T1D and T2D. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Fracture Risk in Patients with Hypoparathyroidism.

To summarize the recently published scientific evidence on fracture risk in hypoparathyroidism. Hypoparathyroidism is characterized by a low bone turnover and a high bone mineral density. Data on fracture risk are sparse and due to the rarity of the disease, available studies have only been able to include relatively few patients. Risk of non-vertebral fractures does not seem to be affected to any major degree, although epidemiological studies suggest a decreased risk of fractures at the humerus in postsurgical hypoparathyroidism, whereas an increased risk of fractures at the upper arm has been shown in non-surgical hypoparathyroidism. Several, but not all, studies have also pointed towards an increased risk of vertebral fractures, especially in non-surgical hypoparathyroidism. Fractures at the appendicular skeleton do not seem to be of specific concern in hypoparathyroidism, but emerging data suggest an increased risk of vertebral fractures, which needs to be clarified further in upcoming studies.

Romosozumab Efficacy in Postmenopausal Women With No Prior Fracture Who Fulfill Criteria for Very High Fracture Risk

ObjectiveWe evaluated the efficacy of romosozumab in women from FRAME who had no prior fracture but met other criteria for very high fracture risk (VHFR). MethodsIn FRAME, postmenopausal women received romosozumab or placebo for 12 months (year 1) followed by denosumab for 12 months (year 2). In this post hoc analysis, we applied the following criteria from the American Association of Clinical Endocrinology to define VHFR: lumbar spine or total hip T-score <−3.0 and/or Fracture Risk Assessment Tool probability of major osteoporotic fracture >30% or hip fracture >4.5% to women with no fracture history at baseline (no fracture-VHFR [NF-VHFR]). Incidence of new vertebral, clinical, and nonvertebral fractures and mean bone mineral density (BMD) percentage change from baseline were assessed at years 1 and 2. ResultsOf the 7180 women in FRAME, 2825 were included in the NF-VHFR subgroup analysis. At year 1, romosozumab versus placebo reduced the incidence of new vertebral fracture (relative risk reduction [RRR]: 76%), clinical fracture (RRR: 60%), and nonvertebral fracture (RRR: 54%) (all P <.05). This fracture reduction was maintained through year 2 in women receiving the romosozumab-to-denosumab sequence versus the placebo-to-denosumab sequence for new vertebral, clinical, and nonvertebral fractures (RRR: 77%, 54%, and 46%, respectively; all P <.05). The mean BMD changes in both treatment groups were similar to those in the overall FRAME population at years 1 and 2. ConclusionRomosozumab significantly reduced vertebral, clinical, and nonvertebral fracture risk and increased the BMD more than placebo in women at VHFR.

Treatment options for postmenopausal osteoporosis

Osteoporosis is a systemic skeletal disease, characterized by a decrease of bone mass and bone quality, with a subsequent reduction of bone strenght and an increased risk of fracture. Hormone Therapy for menopausal women can significantly prevent osteopenia and osteoporosis, thus reducing the fracture risk. The use of HT, according to guidelines, is for postmenopausal women within 10 years since last menstruation or under the age of 60 years. Only HT at standard dose is able to reduce the fracture risk, while low-dose HT can prevent bone loss. Estrogens (with and without the addition of a progestin) and tibolone showed a fracture risk reduction effect. Also Tissue Selective Estrogen Complex (TSEC) can reduce the bone loss in postmenopause. For women without climacteric symptoms (as hot flushes and/or night sweats) the use of Selective Estrogen Receptor Modulators (SERMs) can be indicated, with a reduction of risk of vertebral fracture (for raloxifene and bazedoxifene), and non-vertebral fracture in high-risk women (for bazedoxifene). In more advence ages, antiresoptive agents as Bisphosphonates (Alendronate, Risedronate, Ibandronate and Zoledronate) can reduce the risk of vertebral, non-vertebral and hip fracture risk. Denosumab (DMAB), monoclonal antibobody against Rank-ligand (RANKL), providing an increased bone mass, significantly decreases risk of vertebral, non-vertebral and hip fracture. A drug holiday or treatment interruption is not recommended with DMAB, and DMAB dosing should not stopped without subsequent antiresorptive or other therapy to prevent a "rebound effect" with a possible increased risk of multiple vertebral fracture. Teriparatide (fraction 1-34 of recombinant PTH, administered daily 20 mcg sc) can stimulate osteoblast activity, with an important increase of bone mass and a significant reduction of risk of vertebral fracture, and of multiple vertebral fractures, but also of non-vertebral fragility fracture. Romosozumab (RMZ, adimnistered monlty 210 mg sc), is a bone-forming monoclonal antibody that binds to and inhibits sclerostin, with a dual effect of increasing bone formation and decreasing bone resorption. RMZ has showed to give marked increases in spine and hip bone density after 1 year of administration, also reducing fracture risk. The differences among the various treatments is the basis for the individualization of osteoporosis treatment, according to combination and/or sequential regimens of administration.

Combined and sequential therapies with anabolic and antiresorptive drugs in the management of patients with postmenopausal osteoporosis

The aim of osteoporosis therapy is to reduce the increased fracture risk associated with osteoporosis-related bone fragility. Prevention of fragility fracture relies on balanced nutrition, weight-bearing and balance-improving physical exercises, and pharmacological therapies. Among the latter, the antiresorptive drugs are the most widely used. Bone formation stimulators (anabolics) are second line-therapy with reversible effects once discontinued. For patients at very high risk or imminent risk of fracture, the question arises of whether combining drugs with different modes of action, or using sequential regimens with these agents, could achieve early, higher-magnitude antifracture efficacy than is obtained with usual antiresorptives, and sustained antifracture efficacy. As regards combination therapies, until we have clear evidence that using drugs together provides greater fracture risk reduction than monotherapy, these therapies are not recommended. Anabolic treatments like teriparatide, the amino-terminal fragment of parathyroid hormone, abaloparatide, an analog of parathyroid hormone related protein, and romosozumab, the monoclonal antibody against sclerostin, decrease vertebral and non-vertebral fracture risk and are more efficacious in fracture risk reduction than antiresorptives, as shown in head-to-head trials. However, an anabolic agent should be followed by an antiresorptive drug to maintain and even further increase its antifracture efficacy, which is otherwise rapidly reversible. Because of their early, high-magnitude and sustained antifracture efficacy, such sequential regimens should become the standard of care for patients at very high or imminent risk of fracture.

Abstract #1403811: Rapidly Progressive Aortic Stenosis After Teriparatide Initiation: A Rare Case

Recombinant Parathyroid Hormone (rPTH) or Teriparatide is frequently used to manage severe osteoporosis due to its anabolic mode of action particularly in patients who are at a high risk of vertebral and non-vertebral fractures. Aortic valve stenosis is a common valve condition seen in the older population. There are multiple etiologies for aortic stenosis, but drug induced aortic stenosis is rare. Moreover, its natural history includes gradual progression towards severity. We present an interesting case of rapidly progressive aortic stenosis after teriparatide initiation. An 84-year-old female with history of hypertension, hyperlipidemia, atrial fibrillation presented to the endocrine clinic for management of osteoporosis. She was diagnosed with osteoporosis in 2000 at age 62. Initial etiology was assumed to be post-menopausal and was treated with oral bisphosphonates. As she had compression fractures of her spine while on treatment, secondary causes of osteoporosis were explored, and she was found to have primary hyperparathyroidism. Her labs were significant for PTH-84 pg/ml, Ca-10.8 mg/dl. She underwent parathyroidectomy in 2016 with normalization of PTH and calcium. After her surgery, she was treated with denosumab infusions every 6 months. She did well till June 2021. Her bone mineral density scores were stable throughout this period. At this point, she suffered bilateral atypical femoral fractures and was thought to be due to chronic anti-resorptive therapy. We stopped denosumab and transitioned her to teriparatide daily injections. She did well for 1 year but then presented to us for management in Aug 2022 prior to valve replacement for severe aortic stenosis. Her labs were significant for normal calcium, 25-hydroxy vitamin D and phosphorus levels. On reviewing her echocardiograms prior to and after initiation of teriparatide we found a rapid progression of her aortic stenosis from moderate to severe, based on mean gradients and peak velocities, over a span of 7 months. Natural progression of aortic stenosis from mild to severe happens over several years (mean duration-5 years), not just a few months. One possible explanation for this rapid progression seen in our patient is due to the presence of osteoblast like cells (arising from vascular endothelial cell precursor cells) in the aortic valve which appear to be stimulated by PTH and hence valve calcification/stenosis. On a thorough review of literature there were no clinical studies that have reported aortic stenosis progression from teriparatide use. To our knowledge, there was a single case report that reported the same phenomenon in Israel. As a result, we wanted to educate the community about the possible association between teriparatide use and worsening aortic stenosis in certain cases. Performing serial echocardiograms in high-risk patients and involving cardiology for early diagnosis and management is essential.

Safety of Sodium-Glucose Cotransporter-2 Inhibitors in Patients with CKD and Type 2 Diabetes: Population-Based US Cohort Study.

Limited information exists regarding the safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with CKD treated in routine care. We evaluated the safety of SGLT2i in patients with CKD and type 2 diabetes treated in US routine practice. Using claims data from Medicare and two large US commercial databases (April 2013-December 2021), we included 96,128 adults with CKD stages 3-4 and type 2 diabetes who newly filled prescriptions for SGLT2i versus glucagon-like peptide-1 receptor agonists (GLP-1RA). Safety outcomes included diabetic ketoacidosis (DKA), lower limb amputations, nonvertebral fractures, genital infections, hypovolemia, AKI, hypoglycemia, and severe urinary tract infections (UTIs). Hazard ratios (HRs) and incidence rate differences per 1000 person-years were estimated after 1:1 propensity score matching, adjusted for >120 baseline characteristics. Compared with GLP-1RA, SGLT2i initiators had a higher risk of nonvertebral fractures (HR, 1.30; 95% confidence interval [CI], 1.03 to 1.65]; incidence rate difference, 2.13 [95% CI, 0.28 to 3.97]), lower limb amputations (HR, 1.65 [95% CI, 1.22 to 2.23]; incidence rate difference, 2.46 [95% CI, 1.00 to 3.92]), and genital infections (HR, 3.08 [95% CI, 2.73 to 3.48]; incidence rate difference, 41.26 [95% CI, 37.06 to 45.46]). Similar risks of DKA (HR, 1.07 [95% CI, 0.74 to 1.54]; incidence rate difference, 0.29 [95% CI, -0.89 to 1.46]), hypovolemia (HR, 0.99 [95% CI, 0.86 to 1.14]; incidence rate difference, 0.20 [95% CI, -2.85 to 3.25]), hypoglycemia (HR, 1.08 [95% CI, 0.92 to 1.26]; incidence rate difference, 1.46 [95% CI, -1.31 to 4.23]), and severe UTI (HR, 1.02 [95% CI, 0.87 to 1.19]; incidence rate difference, 0.35 [95% CI, -2.51 to 3.21]) were observed. SGLT2i had lower risk for AKI (HR, 0.93 [95% CI, 0.87 to 0.99]; incidence rate difference, -6.75 [95% CI, -13.69 to 0.20]). In US patients with CKD and type 2 diabetes receiving routine care, SGLT2i use was associated with higher risks of genital infections and potentially lower limb amputations and nonvertebral fractures.

Occurrence and relative risks for non-vertebral fractures in patients with ankylosing spondylitis compared with the general population: a register-based study from Sweden

ObjectivesTo estimate the incidence of non-vertebral fractures in ankylosing spondylitis (AS) compared with the general population.MethodsNationwide register-based cohort study including patients with AS (n=11 611, 65% men, mean age 48...

Medication holidays in osteoporosis: evidence-based recommendations from the Italian guidelines on 'Diagnosis, risk stratification, and continuity of care of fragility fractures' based on a systematic literature review.

Noncommunicable, chronic diseases need pharmacological interventions for long periods or even throughout life. The temporary or permanent cessation of medication for a specific period, known as a 'medication holiday,' should be planned by healthcare professionals. We evaluated the association between continuity (adherence or persistence) of treatment and several outcomes in patients with fragility fractures in the context of the development of the Italian Guidelines. Systematic review. We systematically searched PubMed, Embase, and the Cochrane Library up to November 2020 for randomized clinical trials (RCTs) and observational studies that analyzed medication holidays in patients with fragility fracture. Three authors independently extracted data and appraised the risk of bias of the included studies. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation methodology. Effect sizes were pooled in a meta-analysis using random effects models. Primary outcomes were refracture and quality of life; secondary outcomes were mortality and treatment-related adverse events. Six RCTs and nine observational studies met our inclusion criteria, ranging from very low to moderate quality. The adherence to antiosteoporotic drugs was associated with a lower risk of nonvertebral fracture [relative risk (RR) 0.42, 95% confidence interval (CI) 0.20-0.87; three studies] than nonadherence, whereas no difference was detected in the health-related quality of life. A reduction in refracture risk was observed when continuous treatment was compared to discontinuous therapy (RR 0.49, 95% CI 0.25-0.98; three studies). A lower mortality rate was detected for the adherence and persistence measures, while no significant differences were noted in gastrointestinal side effects in individuals undergoing continuous versus discontinuous treatment. Our findings suggest that clinicians should promote adherence and persistence to antiosteoporotic treatment in patients with fragility fractures unless serious adverse effects occur.

Supplemental Vitamin D Doesn't Reduce Risk of Fracture in Healthy Older Adults.

According to this study: In a study of healthy midlife and older adults who weren't recruited based on vitamin D deficiency, low bone mass, or osteoporosis, supplemental vitamin D didn't lower the risk of total, nonvertebral, or hip fractures compared with placebo.Only one dose of vitamin D was evaluated, and the study results may not be generalizable to adults who have osteoporosis.

Romosozumab efficacy and safety in European patients enrolled in the FRAME trial

SummaryIn this post hoc analysis, we assessed romosozumab efficacy and safety in European patients enrolled in FRAME. Romosozumab treatment through 12 months, followed by denosumab for a further 24 months, resulted in early and sustained risk reduction for major fracture categories, associated with large gains in bone mineral density.IntroductionIn the multinational FRAME phase 3 trial of romosozumab in postmenopausal women with osteoporosis, marked differences between clinical and non-vertebral fracture outcomes were observed among patients from Central and Southern America versus rest of world. This post hoc analysis assessed romosozumab efficacy and safety in European patients enrolled in the FRAME trial and extension study.MethodsIn FRAME (NCT01575834), patients were randomised 1:1 to romosozumab 210 mg or placebo monthly (QM) for 12 months, followed by open-label denosumab 60 mg Q6M to month 36, including a 12-month extension study. We report incidence of major fracture outcomes, bone mineral density (BMD) change from baseline and safety for European patients enrolled in FRAME.ResultsIn FRAME, 3013/7180 (41.96%) patients were European; 1494 received romosozumab and 1519 received placebo. Through 12 months, romosozumab reduced fracture risk versus placebo for non-vertebral fracture (1.4% versus 3.0%; p = 0.004), clinical fracture (1.4% versus 3.6%; p < 0.001), new vertebral fracture (0.4% versus 2.1%; p < 0.001) and major osteoporotic fracture (0.9% versus 2.8%; p < 0.001), with results sustained through 36 months following transition to denosumab. Hip fractures were numerically reduced with romosozumab at month 12 (0.2% versus 0.6%; p = 0.092). Romosozumab increased BMD versus placebo at month 12; all patients in the romosozumab and placebo groups experienced further increases by month 36 after transition to denosumab. Adverse events were balanced between groups.ConclusionsAmong European patients in FRAME, romosozumab resulted in early and sustained risk reduction for all major fracture categories, associated with large BMD gains that continued after transition to denosumab.