Weight loss in men in late life and bone strength and microarchitecture: a prospective study.

Weight loss in men in late life was associated with lower bone strength. In contrast, weight gain was not associated with a commensurate increase in bone strength. Future studies should measure concurrent changes in weight and parameters of bone strength and microarchitecture and evaluate potential causal pathways underlying these associations. INTRODUCTION: Our aim was to determine associations of weight loss with bone strength and microarchitecture. METHODS: We used data from 1723 community-dwelling men (mean age 84.5 years) who attended the MrOS study Year (Y) 14 exam and had high-resolution peripheral quantitative computed tomography (HR-pQCT) scans at ≥ 1 skeletal sites (distal tibia, distal radius, or diaphyseal tibia). Weight change from Y7 to Y14 exams (mean 7.3 years between exams) was classified as moderate weight loss (loss ≥ 10%), mild weight loss (loss 5 to < 10%), stable weight (< 5% change), or weight gain (gain ≥ 5%). Mean HR-pQCT parameters (95%CI) were calculated by weight change category using linear regression models adjusted for age, race, site, health status, body mass index, limb length, and physical activity. The primary outcome measure was estimated failure load. RESULTS: There was a nonlinear association of weight change with failure load at each skeletal site with different associations for weight loss vs. weight gain (p < 0.03). Failure load and total bone mineral density (BMD) at distal sites were lower with greater weight loss with 7.0-7.6% lower failure loads and 4.3-5.8% lower BMDs among men with moderate weight loss compared to those with stable weight (p < 0.01, both comparisons). Cortical, but not trabecular, BMDs at distal sites were lower with greater weight loss. Greater weight loss was associated with lower cortical thickness at all three skeletal sites. CONCLUSION: Weight loss in men in late life is associated with lower peripheral bone strength and total BMD with global measures reflecting cortical but not trabecular parameters.

Predictors of change of trabecular bone score (TBS) in older men: results from the Osteoporotic Fractures in Men (MrOS) Study.

Among older men, characteristics that predict longitudinal changes in trabecular bone score (TBS) are different from characteristics that predict changes in bone mineral density (BMD). Most notably, weight loss is strongly associated with concomitant loss in BMD but with concomitant increases in TBS, when measured on Hologic densitometers. INTRODUCTION: Our objective was to compare and contrast predictors of changes in TBS, total hip BMD, and lumbar spine BMD. METHODS: Our study population was 3969 Osteoporotic Fractures in Men (MrOS) cohort participants (mean age 72.8 years) with repeat measures of TBS, lumbar spine and total hip BMD, body mass index (BMI) less than 37 kg/m2, and no use of bisphosphonate or glucocorticoid medications. TBS was scored (Med-Imaps Software version 2.1) and BMD measured on Hologic densitometers. RESULTS: One thousand four hundred forty-four men had a TBS decrease > 0.04 units (estimated least significant change for TBS), 795 men had a TBS increase > 0.04 units, and 1730 men had TBS change ≤ 0.04 units over mean follow-up of 4.6 years. Older age was not associated with TBS change, but was associated with greater decline in lumbar spine and total hip BMD. Compared to stable weight, > 10% weight loss was strongly associated with an increase in TBS [effect size = 1.24 (95% CI 1.12, 1.36)] and strongly associated with a decrease in total hip BMD [- 1.16 (95% CI - 1.19, - 1.03)]. Other predictors discordant for longitudinal changes of TBS and BMD included baseline BMI, walk speed, and ACE inhibitor use. CONCLUSIONS: Predictors of changes in TBS are different from predictors of changes in lumbar spine and total hip BMD. At least when assessed on Hologic densitometers, weight loss is associated with subsequent declines in spine and total hip BMD but subsequent increase in TBS. Faster walk speed may protect against loss of hip BMD, but is not associated with longitudinal changes of TBS.

High dairy protein intake is associated with greater bone strength parameters at the distal radius and tibia in older men: a cross-sectional study.

Dairy protein but not plant protein was associated with bone strength of the radius and tibia in older men. These results are consistent with previous results in women and support similar findings related to fracture outcomes. Bone strength differences were largely due to thickness and area of the bone cortex. INTRODUCTION: Our objective was to determine the association of protein intake by source (dairy, non-dairy animal, plant) with bone strength and bone microarchitecture among older men. METHODS: We used data from 1016 men (mean 84.3 years) who attended the Year 14 exam of the Osteoporotic Fractures in Men (MrOS) study, completed a food frequency questionnaire (500-5000 kcal/day), were not taking androgen or androgen agonists, and had high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the distal radius and distal or diaphyseal tibia. Protein was expressed as percentage of total energy intake (TEI); mean ± SD for TEI = 1548 ± 607 kcal/day and for total protein = 16.2 ± 2.9%TEI. We used linear regression with standardized HR-pQCT parameters as dependent variables and adjusted for age, limb length, center, education, race/ethnicity, marital status, smoking, alcohol intake, physical activity level, corticosteroids use, supplement use (calcium and vitamin D), and osteoporosis medications. RESULTS: Higher dairy protein intake was associated with higher estimated failure load at the distal radius and distal tibia [radius effect size = 0.17 (95% CI 0.07, 0.27), tibia effect size = 0.13 (95% CI 0.03, 0.23)], while higher non-dairy animal protein was associated with higher failure load at only the distal radius. Plant protein intake was not associated with failure load at any site. CONCLUSION: The association between protein intake and bone strength varied by source of protein. These results support a link between dairy protein intake and skeletal health, but an intervention study is needed to evaluate causality.

Injectable dual-gelling cell-laden composite hydrogels for bone tissue engineering.

The present work investigated the osteogenic potential of injectable, dual thermally and chemically gelable composite hydrogels for mesenchymal stem cell (MSC) delivery in vitro and in vivo. Composite hydrogels comprising copolymer macromers of N-isopropylacrylamide were fabricated through the incorporation of gelatin microparticles (GMPs) as enzymatically digestible porogens and sites for cellular attachment. High and low polymer content hydrogels with and without GMP loading were shown to successfully encapsulate viable MSCs and maintain their survival over 28 days in vitro. GMP incorporation was also shown to modulate alkaline phosphatase production, but enhanced hydrogel mineralization along with higher polymer content even in the absence of cells. Moreover, the regenerative capacity of 2 mm thick hydrogels with GMPs only, MSCs only, or GMPs and MSCs was evaluated in vivo in an 8 mm rat critical size cranial defect for 4 and 12 weeks. GMP incorporation led to enhanced bony bridging and mineralization within the defect at each timepoint, and direct bone-implant contact as determined by microcomputed tomography and histological scoring, respectively. Encapsulation of both GMPs and MSCs enabled hydrogel degradation leading to significant tissue infiltration and osteoid formation. The results suggest that these injectable, dual-gelling cell-laden composite hydrogels can facilitate bone ingrowth and integration, warranting further investigation for bone tissue engineering.

A mathematical model for pulsatile release: controlled release of rhodamine B from UV-crosslinked thermoresponsive thin films.

A controlled drug delivery system fabricated from a thermoresponsive polymer was designed to obtain a pulsatile release profile which was triggered by altering the temperature of the dissolution medium. Two stages of release behaviour were found: fast release for a swollen state and slow (yet significant and non-negligible) release for a collapsed state. Six cycles of pulsatile release between 4 °C and 40 °C were obtained. The dosage of drug (rhodamine B) released in these cycles could be controlled to deliver approximately equal doses by altering the release time in the swollen state. However, for the first cycle, the swollen release rate was found to be large, and the release time could not be made short enough to prevent a larger dose than desired being delivered. A model was developed based on Fick's law which describes pulsatile release mathematically for the first time, and diffusion coefficients at different temperatures (including temperatures corresponding to both the fully swollen and collapsed states) were estimated by fitting the experimental data with the theoretical release profile given by this model. The effect of temperature on the diffusion coefficient was studied and it was found that in the range of the lower critical solution temperature (LCST), the diffusion coefficient increased with decreasing temperature. The model predicts that the effective lifetime of the system lies in the approximate range of 1-42 h (95% of drug released), depending on how long the system was kept at low temperature (below the LCST). Therefore this system can be used to obtain a controllable pulsatile release profile for small molecule drugs thereby enabling optimum therapeutic effects.

Two or three days of ofloxacin treatment for uncomplicated multidrug-resistant typhoid fever in children.

An open randomized comparison of 2 days (Ofx2) versus 3 days (Ofx3) of oral ofloxacin treatment (15 mg/kg/day) was conducted with Vietnamese children between 1 and 15 years of age with suspected typhoid fever. Of 108 children enrolled, 100 were blood culture positive for Salmonella typhi, and 86% of the isolates were multidrug resistant. There were no significant adverse effects. The therapeutic responses were similar in both groups, with mean (+/- standard deviation) fever clearances of 107 +/- 60 h in the Ofx3 group and 100 +/- 64 h in the Ofx2 group (P > 0.2). There were six "clinical" failures in the Ofx2 group and two clinical failures in the Ofx3 group (P > 0.2), in which fever and symptoms persisted for more than 1 week after the start of treatment, but only one of these was culture positive (Ofx3). There was one suspected relapse, and one carrier was identified. Short courses of ofloxacin are simple, inexpensive, safe, and effective for the treatment of uncomplicated multidrug-resistant typhoid fever.

Mechanism of action of a cytotonic enterotoxin produced by Aeromonas hydrophila.

In this study, we describe the mechanism of action of a cytotonic enterotoxin produced by two isolates of Aeromonas hydrophila. Isolates SSU and Ah65 are of different origin and both are capable of producing either a cytotoxic enterotoxin or aerolysin. A cytotonic enterotoxin produced by diarrheal isolate SSU, which was purified and characterized in our laboratory, elevated intracellular cAMP and PgE2 levels in cultured Chinese hamster ovary (CHO) cells. Likewise, enterotoxic activity expressed by a cytotonic enterotoxin was detected in the culture filtrate of a fish isolate (Ah65) after cytotoxic activity was neutralized with homologous aerolysin monoclonal antibodies. This cytotonic enterotoxin also elevated intracellular cAMP and PgE2 levels in CHO cells, suggesting a cholera toxin-like mechanism of action for Aeromonas cytotonic enterotoxins.