Effects of Odanacatib on Bone Structure and Quality in Postmenopausal Women With Osteoporosis: 5-Year Data From the Phase 3 Long-Term Odanacatib Fracture Trial (LOFT) and its Extension

Odanacatib (ODN), a selective oral inhibitor of cathepsin K, was an investigational agent previously in development for the treatment of osteoporosis. In this analysis, the effects of ODN on bone remodeling/modeling and structure were examined in the randomized, double-blind, placebo-controlled, event-driven, Phase 3, Long-term Odanacatib Fracture Trial (LOFT; NCT00529373) and planned double-blind extension in postmenopausal women with osteoporosis. A total of 386 transilial bone biopsies, obtained from consenting patients at baseline (ODN n = 17, placebo n = 23), month 24 (ODN n = 112, placebo n = 104), month 36 (ODN n = 42, placebo n = 41), and month 60 (ODN n = 27, placebo n = 20) were assessed by dynamic and static bone histomorphometry. Patient characteristics at baseline and BMD changes over 5 years for this subset were comparable to the overall LOFT population. Qualitative assessment of biopsies revealed no abnormalities. Consistent with the mechanism of ODN, osteoclast number was higher with ODN versus placebo over time. Regarding bone remodeling, dynamic bone formation indices in trabecular, intracortical, and endocortical surfaces were generally similar in ODN-treated versus placebo-treated patients after 2 years of treatment. Regarding periosteal modeling, the proportion of patients with periosteal double labels and the bone formation indices increased over time in the ODN-treated patients compared with placebo. This finding supported the observed numerical increase in cortical thickness at month 60 versus placebo. In conclusion, ODN treatment for 5 years did not reduce bone remodeling and increased the proportion of patients with periosteal bone formation. These results are consistent with the mechanism of action of ODN, and are associated with continued BMD increases and reduced risk of fractures compared with placebo in the LOFT Phase 3 fracture trial. © 2020 American Society for Bone and Mineral Research.     

Small intestinal adenocarcinoma in Crohn's disease: a case-control study

BACKGROUND: Small bowel adenocarcinoma is an uncommon complication of Crohn's disease. We sought to describe the clinical features, outcomes, and risk factors of small bowel adenocarcinoma in Crohn's disease. METHODS: A centralized diagnostic index identified all patients with Crohn's disease with small bowel adenocarcinoma evaluated at our institution between 1976 and 2000, and the medical records were abstracted. Two controls with Crohn's disease were selected for each case, matched by gender and age. RESULTS: Nine cases (four males) were identified. The patients presented with abdominal pain (89%), obstruction (89%), and weight loss (78%). Cancer was located in the ileum in 8 patients (89%) and the jejunum in 1 patient (11%). All cases but 1 had either lymph node involvement or metastasis. All cases had surgery, with 1 receiving adjuvant chemotherapy. No significant risk factors were found. The mortality rates at 1 and 2 years were 42% and 61%. CONCLUSIONS: Small bowel adenocarcinoma is a rare complication of Crohn's disease that typically involves the ileum. Affected patients have symptomatic, advanced malignancies upon diagnosis. No significant risk factors were identified.     

Recent Developments in Metabolic Bone Diseases: a Gnathic Perspective

Metabolic bone diseases often are asymptomatic and progress sub clinically. Many patients present at a late stage with catastrophic skeletal and extra skeletal complications. In this article, we provide an overview of normal bone remodeling and a synopsis of recent developments in the following conditions: osteoporosis, rickets/osteomalacia, endocrine-induced bone disease, chronic kidney disease-mineral bone disorder and Paget’s disease of bone. Our discussion will emphasize the clinical and microscopic manifestations of these diseases in the jaws.     

Beyond individual differences: are working memory and inhibition informative specifiers within ASD?

Findings on working memory (WM) and inhibition in children with autism spectrum disorders (ASD) are contradictory and earlier studies largely ignored individual differences. As WM and inhibition seem to be related, children who experience WM deficits might also experience inhibition deficits. Moreover, these children possibly form a distinct subgroup, differing on other variables, such as cognitive functioning, symptom severity, behavior, and attention deficit hyperactivity disorder (ADHD) characteristics. We studied a large sample of children with and without ASD (8–12 years, IQ > 80) with classic experimental tasks (n-back task, ASD n = 77, control n = 45; stop task, ASD n = 74, control n = 43), and explored individual differences. The ASD group made more errors on the n-back task with increasing WM load, and had longer stop signal reaction times on the stop task when compared with controls. However, only 6 % of the ASD group showed both WM and inhibition deficits, and 71 % showed no deficits. Parents of children with WM and/or inhibition deficits tended to report more conduct problems on the disruptive behavior disorder rating scale. ADHD characteristics did not influence performance. Some children used medication during testing, which seemingly influenced stop task performance, but excluding these data did not change the main findings. Large individual differences in cognitive functioning are present, even within children with ASD with average or above average intelligence. However, whether individual differences in specific cognitive domains, such as WM and inhibition are as informative as individual differences in diagnosis, comorbidity, and general cognitive functioning, calls for future research.     

Dyspareunia and pelvic floor muscle function before and during pregnancy and after childbirth

Introduction and hypothesis

There is limited knowledge on dyspareunia during pregnancy and postpartum and the role of the pelvic floor muscles (PFM) in women with dyspareunia. Aims of the study were to investigate the presence of dyspareunia before and during pregnancy and postpartum, and to compare vaginal resting pressure (VRP), PFM strength, and endurance between women with and those without dyspareunia. It was hypothesized that there is no difference in PFM variables between women with and those without dyspareunia.

Methods

Three hundred nulliparous women participated in this prospective cohort and answered questions about dyspareunia and the level of bother at gestational weeks 22 and 37, 6 and 12 months postpartum, and retrospectively prior to their pregnancies using ICIQ-FLUTSsex. PFM variables were assessed by manometer at gestational week 22, and 6 and 12 months postpartum. Comparisons between groups were analyzed using independent samples t test.

Results

Twenty-eight and 30 % of the women reported dyspareunia at pre-pregnancy and at gestational week 22 respectively. At gestational week 37, and 6 and 12 months postpartum, the percentages were 40, 45, and 33 respectively. No difference in PFM variables was found between women with and those without dyspareunia. Level of bother was higher postpartum than before and during pregnancy.

Conclusions

Symptoms of dyspareunia were common at all time points. No link could be made between PFM function and dyspareunia. Women suffering from dyspareunia postpartum reported it as being bothersome. Our findings suggest that women should be asked about symptoms of dyspareunia related to pregnancy, and that future research should aim for preventative and therapeutic strategies.     

Long-Term Improvements in Pulmonary Function 5 Years After Bariatric Surgery

Background

Obesity is associated with reduced pulmonary function. We evaluated pulmonary function and status of asthma and obstructive sleep apnoea syndrome (OSAS) before and 5 years after bariatric surgery.

Methods

Spirometry was performed at baseline and 5 years postoperatively. Information of asthma and OSAS were recorded. Of 113 patients included, 101 had undergone gastric bypass, 10 duodenal switch and 2 sleeve gastrectomy.

Results

Eighty (71 %) patients were women, mean preoperative age was 40 years and preoperative weight was 133 kg in women and 158 kg in men. Five years postoperatively, weight reduction was 31 % (42 kg; p?<?0.001) in women and 24 % (38 kg; p?<?0.001) in men. Forced expiratory volume in 1 s (FEV1) increased 4.1 % (116 ml; p?<?0.001) in women and 6.7 % (238 ml; p?=?0.003) in men. Forced vital capacity (FVC) increased 5.8 % (209 ml; p?<?0.001) in women and 7.6 % (349 ml; p?<?0.001) in men. Gender and weight loss were independently associated with the improvements in FEV1 and FVC. At follow-up, FEV1 had increased 36 % of the difference towards the estimated normal FEV1, and there was a corresponding 70 % recovery of FVC. These improvements occurred despite an expected decline in pulmonary function by age during the study period. Of the asthmatics and OSAS patients, 48 and 80 %, respectively, were without symptoms 5 years postoperatively.

Conclusions

Pulmonary function measured with spirometry was significantly improved 5 years after bariatric surgery, despite an expected age-related decline during this period. Symptoms of asthma and OSAS also improved.