Treatment patterns in women with postmenopausal osteoporosis using abaloparatide: a real-world observational study.

Review of medical records from 173 women with osteoporosis who received abaloparatide treatment revealed that 96.0% had at least one visit for osteoporosis management and 55.5% had medication support group access. The most common reasons for discontinuing treatment were financial (31.2%) and tolerability (22.8%). Most patients (64.8%) completed treatment as prescribed. PURPOSE: Abaloparatide is approved for the treatment of women with postmenopausal osteoporosis at high risk for fracture. This study evaluated real-world treatment patterns for patients new to abaloparatide, regardless of osteoporosis treatment history. METHODS: Data for patients with ≥ 1 prescription for abaloparatide were collected retrospectively from six academic and clinical practice settings across the US. RESULTS: A total of 173 patients were enrolled (mean [SD] age, 69.8 [7.4] years). At the time of abaloparatide treatment initiation, 78.6% had received other osteoporosis medications. Mean (SD) time from discontinuation of osteoporosis medications prior to initiation of abaloparatide was 1.7 (3.2) years. Twenty-four months of follow-up data from the initiation date of abaloparatide was collected from 94.0% of patients and 6.0% of patients had 12-24 months of follow-up. During the follow-up period, 96.0% of patients had at least one visit for osteoporosis management and 55.5% had access to a medication support program. The median duration of therapy was 18.6 months and 105/162 (64.8%) completed abaloparatide treatment as prescribed. The most common reasons for treatment discontinuation were financial (31.2%) and tolerability (22.8%). Following completion of a course of treatment with abaloparatide, 82/162 (50.6%) patients transitioned to another osteoporosis medication. The median time between abaloparatide treatment course completion and the initiation of follow-on medication was 21 days. CONCLUSION: Most patients completed treatment with abaloparatide as prescribed, and over half continued with an antiresorptive agent. This favorable conduct may be the result of regular follow-up visits and accessibility to both medication and patient support services.

The Effect of Human Growth Hormone Treatment on the Development of Slipped Capital Femoral Epiphysis: A Cohort Analysis With 6 Years of Follow-up.

BACKGROUND: Slipped capital femoral epiphysis (SCFE) is a common hip disorder in adolescents that can result in substantial complications, impacting the quality of life. Human Growth Hormone (HGH) administration may elevate the risk of SCFE, though the relationship remains unclear. Clarifying this association could enable better monitoring and earlier diagnosis of SCFE in patients receiving HGH. The aim of the study is to investigate the association between HGH administration and the incidence of SCFE. METHODS: This retrospective cohort study utilized data from the TriNetX research database from January 2003 to December 2022. The study included 2 cohorts: an HGH cohort including 36,791 patients aged below 18 years receiving HGH therapy and a control group consisting of patients who did not receive HGH therapy. A 1:1 propensity score matching technique was employed to ensure comparability between the HGH and no-HGH cohorts. The primary outcome measure was the development of SCFE identified by International Classification of Diseases codes. For comparative analysis, both risk ratios (RR) and hazard ratios were computed to evaluate the association between HGH therapy and the development of SCFE. RESULTS: The HGH cohort had an increased risk of SCFE compared with the no-HGH cohort (RR: 3.5, 95% CI: 2.073, 5.909, P <0.001) and had an increased hazard of developing SCFE (hazard ratio: 2.627, 95% CI: 1.555, 4.437, P <0.001). Patients with higher exposure to HGH (defined as >10 prescriptions) had an RR of 1.914 (95% CI: 1.160, 3.159, P =0.010) when compared with their counterparts with ≤10 prescriptions. CONCLUSIONS: In the largest study to date, HGH administration was associated with an elevated risk of SCFE in children in a dose-dependent manner. LEVEL OF EVIDENCE: Level III-therapeutic retrospective cohort study.

The Association of Pelvic Bone Mineral Density and With Proximal Femoral and Spine Bone Mineral Density in Post-menopausal Women.

Pelvic fragility fractures result in significant morbidity and their incidence has increased over the past 30 years. One of the main risk factors in skeletal fragility is bone mineral density (BMD). Most of the current literature has focused on understanding spine and hip BMD. We aimed to measure the BMD of pelvis in a cohort of post-menopausal women and compare it to BMD at other skeletal sites. A questionnaire regarding risk factors for osteoporosis was completed by each participant. DXA scan of the pelvis was performed using research software. Three areas of the pelvis corresponding to common fractures were defined on pelvic DXA: R1 = symphysis public, R2 = inferior public rami, R3 = superior public rami. Pelvic BMD was calculated as the average BMD of R1-3. BMD at each location was reported as mean and standard deviation (SD). ANOVA was used to compare BMD between R1-R3 and pelvis, femoral neck, total hip, and spine. Pearson correlation was used to correlate pelvic BMD to BMD of proximal femur and spine. BMD was compared in four participant groups: 1- osteoporosis in spine and hip, 2- osteoporosis in spine only, 3-osteoporosis in hip only, and 4- no osteoporosis in spine and hip. The effect of diabetes and obesity on BMD at various skeletal sites was analyzed. Among the one hundred postmenopausal women enrolled in the study, age was: 64 ± 8, 31% were obese (BMI ≥ 30), and 8% had a diagnosis of type 2 diabetes. Pelvic area R3 had significantly higher BMD than R1 or R2 (p < 0.001). Pelvic BMD (0.50 ± 0.16) was significantly lower than total hip (0.70 ± 0.20) and spine BMD (0.97 ± 0.19) (p < 0.001). Pelvic BMD correlated with BMD at other skeletal locations, with the highest correlation with total hip (total hip: R2: 0.70, femoral neck R2: 0.50, spine R2: 0.65). Pelvic BMD was significantly lower in patients with osteoporosis of both hip and spine compared to the group without osteoporosis at both locations (p = 0.02). Obesity and type 2 diabetes were both associated with significantly higher BMD at pelvis, spine, and total hip. Pelvic BMD is lower than at other skeletal sites and is highly correlated with total hip area bone density. Obesity and type 2 diabetes are associated with higher pelvic BMD. To establish guidelines for the treatment pelvic BMD, studies defining the association of pelvic BMD with pelvic fracture risk are needed.

Abaloparatide Real-World Patient Experience Study.

Despite the availability of various osteoporosis treatments, adherence remains suboptimal. One contributing factor may be patient experience with therapy. This US, multicenter, combined retrospective chart review and patient questionnaire study included postmenopausal women at high risk for fracture and is the first study to describe real-world patient experience with abaloparatide (ABL) injection. Eight geographically diverse secondary care sites in the United States participated (n = 193). Mean ± SD age was 67.4 ±8.62 years. Most patients (86%) were satisfied with the ABL regimen, especially with ease of preparation (82%), ease of storage (87%), and storage convenience (89%), an attribute 83% of the patients thought was important. The majority of patients reported complete satisfaction with the ABL regimen allowing for their ability to conduct daily activities (85%) and convenience to fit into their daily schedule (84%). All reported taking ABL as directed, by injection in the lower abdomen, and 83% of patients reported medium or high adherence. Patients were satisfied with the needle size (76% completely satisfied), and 93% reported never deliberately missing a dose. Although injecting medication (18%) and higher out-of-pocket costs (17%) were deemed the most bothersome attributes, the majority (69%) noted their healthcare team understands how osteoporosis impacts their lives. In multivariable analyses, ease of preparation (OR = 2.62; 95% CI, 1.01-6.81; p = 0.048) and fracture history (OR = 1.72; 95% CI, 1.03-2.86; p = 0.037) were significantly associated with overall satisfaction. Ease of preparation was a predictor of higher satisfaction with treatment convenience (coefficient = 13.60; 95% CI, 8.08-19.12; p = 0.00). Remembering to take the medication was a significant predictor of self-reported adherence (OR = 16.66; 95% CI, 3.30-84.24; p = 0.001). In conclusion, the majority of patients were satisfied with ABL and found it convenient/easy to prepare and store. High self-reported adherence may be associated with positive patient experience including ease of use and adequate support from healthcare providers. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Effect of peripheral neuropathy on bone mineral density in adults with diabetes: A systematic review of the literature and meta-analysis.

INTRODUCTION: Peripheral neuropathy occurs in two thirds of patients with diabetes mellitus (DM). It can lead to severe pathological changes in the feet, and it increases the risk of fracture more than any other diabetic complication. The objective of this review is to analyze available literature on the effect of peripheral neuropathy on BMD of the foot, spine, or hip. We hypothesize that the presence of diabetic neuropathy leads to lower BMD in adults with diabetes. METHODS: Original studies investigating the effects of diabetic neuropathy on bone density were searched for inclusion in this systematic review. Studies were eligible if they met the following criteria: 1) participants included adults with either Type 1 DM or Type 2 DM; 2) Method used for the diagnosis of neuropathy described in the manuscript 3) DXA scan, ultrasound, or CT scan was used to measure proximal femur, spine, or foot bone mineral density were reported, and 4) bone parameters were analyzed based on the presence and absence of neuropathy. RESULTS: Among the 5 studies that met eligibility criteria, 4 did not find a significant effect of neuropathy on BMD. One study showed a significant negative impact of neuropathy on calcaneal BMD in patients with type 1 diabetes. The meta-analysis did not show a significant effect of peripheral neuropathy on BMDs of proximal femur, spine, and calcaneus in diabetic adults. CONCLUSION: Our study shows no evidence that peripheral neuropathy affects bone density or bone turnover in DM. However, this conclusion should be taken with caution since only a very limited number of studies were available for inclusion in the analysis and included both type 1 and type 2 DM patients. Improved measures of peripheral neuropathy and more advanced imaging technologies are needed to better assess the effect of diabetes on bone health.

Vitamin D Status in Children With Forearm Fractures: Incidence and Risk Factors.

INTRODUCTION: The association between vitamin D status and fracture characteristics in children remains ambiguous. We hypothesized that vitamin D deficient or insufficient children would have an increased risk of forearm fractures severe enough to require surgical management. METHODS: One hundred children with low-energy forearm fractures were prospectively enrolled from a single hospital. Each participant answered a questionnaire focusing on the risk factors for vitamin D deficiency. Fractures were categorized as requiring nonsurgical or surgical management. Vitamin D status was based on the measurement of 25-hydroxyvitamin D (25(OH)D) concentration obtained during the clinic visit and compared between the two fracture groups. RESULTS: The cohort exhibited a mean age of 9.8 ± 3.2 years (range: 3-15 years), comprising 65 (65%) men and 35 (35%) women. Overall, mean 25(OH)D was 27.5 ± 8.3 ng/mL. Using the Endocrine Society guidelines, 21% of patients were categorized as "vitamin D deficient" (25(OH)D ≤ 20 ng/mL) and 49% as "vitamin D insufficient" (25(OH)D: 21 to 29 ng/mL). Stratification by intervention revealed a mean 25(OH)D of 23.3 ± 8.8 ng/mL in the surgical group (n = 12) and 28.1 ± 8.1 in the nonsurgical group (n = 88) (P = 0.057). Fifty percent of the surgical group were "vitamin D deficient" compared with 17% of the nonsurgical group (P = 0.017). The relative risk of requiring surgical treatment in children with forearm fracture and vitamin D deficiency (25(OH)D < 20 ng/mL) was 3.8. 25(OH)D level, negatively correlated with body mass index (r = -0.21, P = 0.044); 9 surgical patients were overweight or obese (as defined by the criteria of the Centers for Disease Control and Prevention). 25(OH)D level was significantly lower in non-Caucasians compared with Caucasians (26.0 ± 7.2 versus 32.5 ± 9.9 ng/mL; P = 0.0008). DISCUSSION: Vitamin D deficiency is common in children with forearm fractures and may be a contributing risk factor for forearm fractures requiring surgical management in children. CONCLUSION: Vitamin D deficiency and inefficiency are common in children with low energy forearm fractures, especially in obese children and in fractures requiring surgical treatment.

ATRAID regulates the action of nitrogen-containing bisphosphonates on bone.

Nitrogen-containing bisphosphonates (N-BPs), such as alendronate, are the most widely prescribed medications for diseases involving bone, with nearly 200 million prescriptions written annually. Recently, widespread use of N-BPs has been challenged due to the risk of rare but traumatic side effects such as atypical femoral fracture (AFF) and osteonecrosis of the jaw (ONJ). N-BPs bind to and inhibit farnesyl diphosphate synthase, resulting in defects in protein prenylation. Yet, it remains poorly understood what other cellular factors might allow N-BPs to exert their pharmacological effects. Here, we performed genome-wide studies in cells and patients to identify the poorly characterized gene, ATRAID Loss of ATRAID function results in selective resistance to N-BP-mediated loss of cell viability and the prevention of alendronate-mediated inhibition of prenylation. ATRAID is required for alendronate inhibition of osteoclast function, and ATRAID-deficient mice have impaired therapeutic responses to alendronate in both postmenopausal and senile (old age) osteoporosis models. Last, we performed exome sequencing on patients taking N-BPs that suffered ONJ or an AFF. ATRAID is one of three genes that contain rare nonsynonymous coding variants in patients with ONJ or an AFF that is also differentially expressed in poor outcome groups of patients treated with N-BPs. We functionally validated this patient variation in ATRAID as conferring cellular hypersensitivity to N-BPs. Our work adds key insight into the mechanistic action of N-BPs and the processes that might underlie differential responsiveness to N-BPs in people.

Liraglutide causes large and rapid epicardial fat reduction.

OBJECTIVE: Epicardial adipose tissue (EAT), the visceral fat depot of the heart, is a modifiable cardiovascular risk factor and emerging therapeutic target. Liraglutide, an analog of glucagon-like peptide-1, is indicated for the treatment of type 2 diabetes mellitus. Liraglutide has recently been shown to reduce cardiovascular risk. Nevertheless, whether liraglutide could reduce EAT is unknown. METHODS: To test the hypothesis, a 6-month randomized, open-label, controlled study was performed in 95 type 2 diabetic subjects with body mass index (BMI) ≥27 kg/m2 and hemoglobinA1c ≤8% on metformin monotherapy. Individuals were randomized in two groups to receive additional liraglutide up to 1.8 mg s.c. once daily (n = 54) or to remain on metformin up to 1,000 mg twice daily (n = 41). Ultrasound-measured EAT thickness was measured at baseline and at 3- and 6-month follow-ups. RESULTS: In the liraglutide group, EAT decreased from 9.6 ± 2 to 6.8 ± 1.5 and 6.2 ± 1.5 mm (P < 0.001), accounting for a -29% and -36% of reduction at 3 and 6 months, respectively, whereas there was no EAT reduction in the metformin group; BMI and hemoglobinA1c improved only in the liraglutide group after 6 months. CONCLUSIONS: Liraglutide causes a substantial and rapid EAT reduction. Liraglutide cardiometabolic effects may be EAT-mediated.

Treatment of infected pseudoaneurysm in drug abusers: ligation or reconstruction?

BACKGROUND: Recently, there has been an increase in the incidence of major vascular complications such as infected pseudoaneurysm due to intravenous drug use. OBJECTIVE: For better understanding of the existing controversies regarding the optimal surgical management of infected pseudoaneurysm, the present study was conducted. METHODS: Medical charts of 36 consecutive patients who underwent surgery in Taleghani Hospital, Tehran, Iran from 1996 through 2003, were retrospectively analyzed. RESULTS: We studied the hospital records of 33 cases; two patients had bilaterally infected pseudoaneurysms and one underwent an emergency reoperation. The total number of operations was 36. Eleven cases (30.5%) underwent ileofemoral reconstruction and 25 (69.5%) arteries were ligated. All patients presented with infected femoral or brachial pseudoaneurysms due to intravenous drug abuse. Postoperatively, there was no hemorrhage, vascular thrombosis, amputation, or mortality. Three cases (8%) had incisional infections (2 [18%] after reconstruction and 1 [4%] after ligation operation) and 7 patients (19%) had claudication (all after ligation). CONCLUSION: Ligation is the optimal management for infected pseudoaneurysm, because it is easy, cost-effective, and safe. Reconstruction is not recommended, because of an extended infection at the location of pseudoaneurysm and at the artificial graft site.