The effect of parathyroid hormone on osteogenesis is mediated partly by osteolectin.

We previously described a new osteogenic growth factor, osteolectin/Clec11a, which is required for the maintenance of skeletal bone mass during adulthood. Osteolectin binds to Integrin α11 (Itga11), promoting Wnt pathway activation and osteogenic differentiation by leptin receptor+ (LepR+) stromal cells in the bone marrow. Parathyroid hormone (PTH) and sclerostin inhibitor (SOSTi) are bone anabolic agents that are administered to patients with osteoporosis. Here we tested whether osteolectin mediates the effects of PTH or SOSTi on bone formation. We discovered that PTH promoted Osteolectin expression by bone marrow stromal cells within hours of administration and that PTH treatment increased serum osteolectin levels in mice and humans. Osteolectin deficiency in mice attenuated Wnt pathway activation by PTH in bone marrow stromal cells and reduced the osteogenic response to PTH in vitro and in vivo. In contrast, SOSTi did not affect serum osteolectin levels and osteolectin was not required for SOSTi-induced bone formation. Combined administration of osteolectin and PTH, but not osteolectin and SOSTi, additively increased bone volume. PTH thus promotes osteolectin expression and osteolectin mediates part of the effect of PTH on bone formation.

Resistance Training Reduces Skeletal Muscle Work Efficiency in Weight-Reduced and Non-Weight-Reduced Subjects.

OBJECTIVE: The objective of this study is to determine whether resistance training is similarly effective in reducing skeletal muscle efficiency and increasing strength in weight-reduced and maximal weight subjects. METHODS: This study examined the effects of supervised resistance exercise on skeletal muscle in 14 individuals with overweight and obesity sustaining a 10% or greater weight loss for over 6 months and a phenotypically similar group of 15 subjects who had not reduced weight and were weight stable at their maximal lifetime body weight. We assessed skeletal muscle work efficiency and fuel utilization (bicycle ergometry), strength (dynamometry), body composition (dual energy x-ray absorptiometry), and resting energy expenditure (indirect calorimetry) before and after 12 weeks of thrice-weekly resistance training. RESULTS: Non-weight-reduced subjects were significantly (10%-20%) stronger before and after the intervention than reduced-weight subjects and gained significantly more fat-free mass with a greater decline in percentage of body fat than weight-reduced subjects. Resistance training resulted in similar significant decreases (~10%) in skeletal muscle work efficiency at low-level exercise and ~10% to 20% increases in leg strength in both weight-reduced and non-weight-reduced subjects. CONCLUSIONS: Resistance training similarly increases muscle strength and decreases efficiency regardless of weight loss history. Increased resistance training could be an effective adjunct to reduced-weight maintenance therapy.

Celiac disease: similar presentations in the elderly and young adults.

BACKGROUND/AIMS: Studies have shown that celiac disease can affect individuals in all age groups. However, few studies have described the disease in the elderly. The goal of this study is to characterize celiac disease in the elderly by comparing to a population of young adults with celiac disease. METHODS: Review of a tertiary center database of patients with celiac disease was performed to identify two groups of patients, an elderly cohort ≥ 65 years and a young adult cohort aged 18-30 years, with biopsy-confirmed celiac disease. Information obtained included symptom duration, clinical presentation, small intestinal pathology, associated conditions, and the presence of bone disease. RESULTS: Included in the study were 149 young adult and 125 elderly patients; the latter represented 12.4% of the patients in our database. The duration of symptoms prior to diagnosis was similar, 5.8 ± 12 years and 6.14 ± 12.6 years in the young adult and elderly cohorts, respectively (p = 0.119). There was no significant difference in the mode of presentation of illness. Diarrhea was the main presenting symptom (49% in young adults vs. 50% in the elderly, p = 0.921). There was a similar prevalence of autoimmune disease (19% in young adults vs. 26% in the elderly, p = 0.133). Thyroid disease and neuropathy were more prevalent in the elderly (p = 0.037 and p = 0.023, respectively). The degree of villous atrophy and prevalence of bone disease were similar in each group. CONCLUSIONS: Surprisingly, the presentation of celiac disease both clinically and histologically is similar in elderly and young adult patients. The factors triggering disease at any given age remain unclear and warrant further study.