The long-term skeletal effects of ovariectomy and aging were studied in female Sprague-Dawley rats sacrificed at 270, 370, and 540 days after bilateral ovariectomy (OVX) or sham surgery at 90 days of age. The proximal tibia was processed undecalcified for quantitative bone histomorphometry. For continuity, data from these late time points were combined with previously published data from earlier time points (0-180 days). A biphasic pattern of cancellous bone loss was detected in the proximal tibial metaphysis of OVX rats. An initial, rapid phase of bone loss out to 100 days was followed by an intermediate period of relative stabilization of cancellous bone volume at the markedly osteopenic level of 5-7%. After 270 days, a slow phase of bone loss occurred during which cancellous bone volume declined to 1-2%. Both the initial, rapid phase and the late, slow phase of bone loss in OVX rats were associated with increased bone turnover. In control rats, cancellous bone volume remained constant at 25-30% out to 270 days (12 months of age), then decreased to approximately 10% by 540 days (21 months of age). This age-related bone loss was also associated with increased bone turnover. It is interesting to note that the proximal tibial growth plates were closed in approximately a quarter of the control rats by 15-21 months of age. Our data indicate that a slow rate of bone loss and increased bone turnover persist in OVX rats during the later stages of estrogen deficiency. Therefore, the development of osteopenia is coincident with increased bone turnover in OVX rats as well as in aged, control rats.

Background With approximately 8 hours of one’s waking day spent at work, occupational tasks and environments are important influencers on an individual’s physical activity (PA) and sedentary behaviours. Little research has compared device-measured physical activity, sedentary behaviour and cardiometabolic outcomes between occupational groups. Objective To compare device-measured movement (sedentary time [ST], light intensity physical activity [LPA], moderate-to-vigorous intensity physical activity [MVPA], and steps) across occupations. The secondary objective was to examine whether cardiometabolic and fitness outcomes differed by occupation. Methods Five bibliographic databases were searched to identify all studies which included working age, employed adults from high-income countries, and reported on device-measured movement within occupations. Risk of bias within and across studies was assessed. Results were synthesized using meta-analyses and narrative syntheses. Results The review includes 132 unique studies with data from 15,619 participants. Working adults spent ~ 60% of their working and waking time engaged in sedentary behaviour; a very small proportion (~ 4%) of the day included MVPA. On average, workers accumulated 8124 steps/day. Office and call center workers’ steps/day were among the lowest, while those of postal delivery workers were highest. Office workers had the greatest ST and the lowest time in LPA both at work and during wakeful time. However, office workers had the greatest minutes sent in MVPA during wakeful hours. Laborers had the lowest ST and spent a significantly greater proportion of their work time in LPA and MVPA. Healthcare and protective services workers had higher levels of LPA at work compared to other occupations. Workers in driving-based occupations tended to have a higher body mass index and blood pressure. Conclusion This review identifies that occupational and wakeful time PA and ST differed between occupations. Future studies are needed to assess whether patterns differ by age and sex, describe leisure-time movement and movement patterns, and the relationship with cardiometabolic health. Systematic review registration PROSPERO CRD42017070448 . Electronic supplementary material The online version of this article (10.1186/s12966-019-0790-9) contains supplementary material, which is available to authorized users.

Almost 50 inborn errors of metabolism have been described due to congenital defects in N-linked glycosylation. These phenotypically diverse disorders typically present as clinical syndromes, affecting multiple systems including the central nervous system, muscle function, transport, regulation, immunity, endocrine system, and coagulation. An increasing number of disorders have been discovered using novel techniques that combine glycobiology with next-generation sequencing or use tandem mass spectrometry in combination with molecular gene-hunting techniques. The number of “classic” congenital disorders of glycosylation (CDGs) due to N-linked glycosylation defects is still rising. Eight novel CDGs affecting N-linked glycans were discovered in 2013 alone. Newly discovered genes teach us about the significance of glycosylation in cell–cell interaction, signaling, organ development, cell survival, and mosaicism, in addition to the consequences of abnormal glycosylation for muscle function. We have learned how important glycosylation is in posttranslational modification and how glycosylation defects can imitate recognizable, previously described phenotypes. In many CDG subtypes, patients unexpectedly presented with long-term survival, whereas some others presented with nonsyndromic intellectual disability. In this review, recently discovered N-linked CDGs are described, with a focus on clinical presentations and therapeutic ideas. A diagnostic approach in unsolved N-linked CDG cases with abnormal transferrin screening results is also suggested.

This study was designed to test the hypothesis that endocrine and pharmacological suppressors of bone turnover prevent the development of osteopenia during estrogen deficiency. Sham-operated control and ovariectomized (OVX) rats were treated intermittently with vehicle alone, estrogen, or the diphosphonate compounds etidronate disodium (EHDP) and NE-58095 [2-(3-pyridinyl)2-hydroxyethylidene-1,1-bisphosphonate disodium] for 35 or 70 days after surgery. Their proximal tibiae were processed undecalcified for quantitative bone histomorphometry. Vehicle-treated OVX rats were characterized by decreased cancellous bone volume and 3- to 4-fold increases in osteoblast surface, osteoclast surface, bone formation rate, and bone resorption rate. Treatment of OVX rats with estrogen and NE-58095 provided complete protection against bone loss and significantly depressed all of the above indices of bone turnover. OVX rats treated with EHDP exhibited at least partial protection against bone loss and decreased bone turnover. EHDP induced a mild mineralization defect, as indicated by a prolonged mineralization lag time at the tibial endocortical surface. The new diphosphonate compound NE-58095 did not impair bone mineralization. Our results indicate that endocrine and pharmacological suppressors of bone turnover prevent the development of osteopenia during the early stages of estrogen deficiency. If confirmed by clinical trials in humans, diphosphonate compounds may prove to be an alternative to estrogen for the prevention of postmenopausal bone loss.