Zoledronate treatment duration is linked to bisphosphonate‐related osteonecrosis of the jaw prevalence in rice rats with generalized periodontitis

ObjectivesTo determine the extent that zoledronate (ZOL) dose and duration is associated with bisphosphonate‐related osteonecrosis of the jaw (BRONJ) prevalence in rice rats with generalized periodontitis (PD), characterize structural and tissue‐level features of BRONJ‐like lesions in this model, and examine the specific anti‐resorptive role of ZOL in BRONJ.Materials and MethodsRice rats (n = 228) consumed high sucrose‐casein diet to enhance generalized PD. Groups of rats received 0, 8, 20, 50 or 125 µg/kg IV ZOL/4 weeks encompassing osteoporosis and oncology ZOL doses. Rats from each dose group (n = 9–16) were necropsied after 12, 18, 24 and 30 weeks of treatment. BRONJ‐like lesion prevalence and tissue‐level features were assessed grossly, histopathologically and by MicroCT. ZOL bone turnover effects were assessed by femoral peripheral quantitative computed tomography, serum bone turnover marker ELISAs and osteoclast immunolabelling.ResultsPrevalence of BRONJ‐like lesions was significantly associated with (a) ZOL treatment duration, but plateaued at the lowest oncologic dose, and (b) there was a similar dose‐related plateau in the systemic anti‐resorptive effect of ZOL. ZOL and BRONJ‐like lesions also altered the structural and tissue‐level features of the jaw.ConclusionThe relationship between BRONJ‐like lesion prevalence and ZOL dose and duration varies depending on the co‐ or pre‐existing oral risk factor. At clinically relevant doses of ZOL, BRONJ‐like lesions are associated with anti‐resorptive activity.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149302/1/odi13052.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149302/2/odi13052_am.pd

A rodent model of caloric restriction using bone mass, microarchitecture, and stable isotope ratios: implications for revealing chronic food insufficiency in archaeological populations

One important question with respect to past health and disease is the identification of patterns of caloric inadequacies. Given the substantial literature (animal and human) linking caloric inadequacy to reduced bone mass, microarchitectural deterioration, and changes in stable isotope values, we utilized a rodent model to examine whether integrating these data might help discern episodes of caloric insufficiency. Bone stable isotope values and bone morphometric data were analyzed from a sample of adult male rats in a controlled feeding study. Three-dimensional micro-computed tomography revealed substantial impacts to femoral bone mass and microarchitecture among calorie-restricted animals compared to controls, and we found significant correlations between those parameters and δ13Capatite values. Results support consideration of caloric inadequacy in differential diagnoses of bone loss within archaeological populations, and suggest that similar relationships among stable isotope signatures and bone morphometric parameters delineated within past human populations may help illuminate periods of food insufficiency

Activity-Based Physical Rehabilitation with Adjuvant Testosterone to Promote Neuromuscular Recovery after Spinal Cord Injury

Neuromuscular impairment and reduced musculoskeletal integrity are hallmarks of spinal cord injury (SCI) that hinder locomotor recovery. These impairments are precipitated by the neurological insult and resulting disuse, which has stimulated interest in activity-based physical rehabilitation therapies (ABTs) that promote neuromuscular plasticity after SCI. However, ABT efficacy declines as SCI severity increases. Additionally, many men with SCI exhibit low testosterone, which may exacerbate neuromusculoskeletal impairment. Incorporating testosterone adjuvant to ABTs may improve musculoskeletal recovery and neuroplasticity because androgens attenuate muscle loss and the slow-to-fast muscle fiber-type transition after SCI, in a manner independent from mechanical strain, and promote motoneuron survival. These neuromusculoskeletal benefits are promising, although testosterone alone produces only limited functional improvement in rodent SCI models. In this review, we discuss the (1) molecular deficits underlying muscle loss after SCI; (2) independent influences of testosterone and locomotor training on neuromuscular function and musculoskeletal integrity post-SCI; (3) hormonal and molecular mechanisms underlying the therapeutic efficacy of these strategies; and (4) evidence supporting a multimodal strategy involving ABT with adjuvant testosterone, as a potential means to promote more comprehensive neuromusculoskeletal recovery than either strategy alone

The effects of short-term alpha-ketoisocaproic acid supplementation on exercise performance: a randomized controlled trial

Abstract Background This study examined the efficacy of short-term alpha-ketoisocaproic acid (KIC) monotherapy supplementation immediately prior to moderate- and high-intensity single bout exercise performance. Methods Thirteen resistance trained men (22.8 ± 2.5 years; 81.6 ± 12.6 kg) participated in a prospective, randomized, double blind, placebo controlled crossover experiment. Each subject completed one familiarization and four experimental trials with either 1.5 g or 9.0 g of either KIC or isocaloric placebo control (CONT), following an overnight fast. During the experimental trials, subjects consumed the supplement regimen and then completed leg and chest press repetitions to failure and 30 s of repeated maximal vertical jumping (VJ) on a force plate. Results In this treatment regimen, no significant differences (p > 0.05) were observed between dosages or conditions for leg press (low CONT = 19.8 ± 0.4 SEM, low KIC = 21.0 ± 0.5, high CONT = 20.1 ± 0.3, high KIC = 22.4 ± 0.6) or chest press (low CONT = 18.1 ± 0.2, low KIC = 18.5 ± 0.3, high CONT = 17.8 ± 0.3, high KIC = 18.0 ± 0.3) repetitions to failure. Additionally, no significant differences were observed for peak or mean VJ performance (low CONT = 34.6 ± 2.2 cm and 28.6 ± 1.8 cm; low KIC = 35.6 ± 2.0 cm and 29.4 ± 1.6 cm; high CONT = 35.7 ± 2.1 cm and 29.4 ± 1.7 cm; high KIC = 34.8 ± 2.3 cm and 28.3 ± 1.7 cm), respectively. Conclusion Based on our results, we conclude that acute KIC ingestion by itself with no other ergogenic supplement, immediately prior to exercise, did not alter moderate- nor high-intensity single-bout exercise performance in young resistance-trained males. This study addressed single-dose single-bout performance events; the efficacy of KIC monotherapy supplementation on repeated high-intensity exercise bouts and long-term exercise training remains unknown.</p