Acute and severe trabecular bone loss in a rat model of critical illness myopathy.

Prolonged mechanical ventilation for critically ill patients with respiratory distress can result in severe muscle wasting with preferential loss of myosin. Systemic inflammation triggered by lung mechanical injury likely contributes to this myopathy, although the exact mechanisms are unknown. In this study, we hypothesized that muscle wasting following mechanical ventilation is accompanied by bone loss. The objective was to determine the rate, nature, and extent of bone loss in the femora of rats ventilated up to 10 days and to relate the bone changes to muscle deterioration. We have developed a rat model of ventilator-induced muscle wasting and established its feasibility and clinical validity. This model involves pharmacologic paralysis, parenteral nutrition, and continuous mechanical ventilation. We assessed the hindlimb muscle and bone of rats ventilated for 0, 2, 5, 8, and 10 days. Routine histology, microCT, and biomechanical evaluations were performed. Hindlimb muscles developed changes consistent with myopathy, whereas the femurs demonstrated a progressive decline in trabecular bone volume, mineral density, and microarchitecture beginning Day 8 of mechanical ventilation. Biomechanical testing showed a reduction in flexural strength and stiffness on Day 10. The bone changes correlated with the loss of muscle mass and myosin. These results demonstrate that mechanical ventilation leads to progressive trabecular bone loss parallel to muscle deterioration. The results of our study suggest that mechanically ventilated patients may be at risk of compromised bone integrity and muscle weakness, predisposing to post-ventilator falls and fractures, thereby warranting interventions to prevent progressive bone and muscle decline.

A comparison of alendronate to varying magnitude PEMF in mitigating bone loss and altering bone remodeling in skeletally mature osteoporotic rats.

Pulsed electromagnetic field (PEMF) treatments stimulate bone formation activities though further work is needed to optimize its therapeutic benefit. PEMF can generate local potential gradients and electric currents that have been suggested to mimic bone electrochemical responses to load. In line with this reasoning, a recent publication reported that PEMF application on isolated bone tissue induced detectable micro-vibrations (doi:https://doi.org/10.1109/TMAG.2016.2515069). To determine the ability of PEMF to intervene in a rat model of osteoporosis, we tested its effect on trabecular and cortical bone following ovariectomy. Four PEMF treatments, with increasing sinusoidal amplitude rise with time (3850 Hz pulse frequency and 15 Hz repetition rate at 10 tesla/sec (T/s), 30 T/s, 100 T/s, or 300 T/s), were compared to the efficacy of an osteoporosis drug, alendronate, in reducing levels of trabecular bone loss in the proximal tibia. Herein, the novel findings from our study are: (1) 30 T/s PEMF treatment approached the efficacy of alendronate in reducing trabecular bone loss, but differed from it by not reducing bone formation rates; and (2) 30 T/s and 100 T/s PEMF treatments imparted measurable alterations in lacunocanalicular features in cortical bone, consistent with osteocyte sensitivity to PEMF in vivo. The efficacy of specific PEMF doses may relate to their ability to modulate osteocyte function such that the 30 T/s, and to a lesser extent 100 T/s, doses preferentially antagonize trabecular bone resorption while stimulating bone formation. Thus, PEMF treatments of specific magnetic field magnitudes exert a range of measurable biological effects in trabecular and cortical bone tissue in osteoporotic rats.

Longitudinal Association Between Trabecular Bone Loss and Disease Activity in Axial Spondyloarthritis: A 4-year Prospective Study.

OBJECTIVE: To investigate whether trabecular bone loss is longitudinally associated with disease activity measures in patientswith axial spondyloarthritis (axSpA). METHODS: Data from patients enrolled in the Incheon Saint Mary's axSpA prospective observational cohort were evaluated. Trabecular bone loss was assessed using the trabecular bone score (TBS). The relationship between TBS and disease activity measures [Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP)] was investigated using generalized estimating equation (GEE) models. RESULTS: Four-year followup data from 240 patients (80% males, mean age 37 ± 12 yrs) were evaluated. At baseline, higher disease activity according to ASDAS-ESR and ASDAS-CRP showed a trend toward lower TBS (p = 0.003 and p = 0.016, respectively). Univariate GEE analyses showed a significant association between TBS and disease activity measures over time, with the exception of BASDAI. Univariate analysis showed a longitudinal association between TBS and age, smoking, and spinal structural damage. In multivariate GEE analysis, ASDAS-ESR, ASDAS-CRP, ESR, and CRP were longitudinally associated with TBS after adjustment for confounding factors. ASDAS scores and inflammatory markers were longitudinally associated with TBS in patients with ankylosing spondylitis (AS; 79%), but not in patients with nonradiographic axSpA (nr-axSpA). BASDAI scores showed no relationship with TBS in either the AS or nr-axSpA groups. CONCLUSION: Trabecular bone loss in patients with axSpA, assessed using the TBS, showed a longitudinal association with ASDAS scores and inflammatory markers.

Trabecular bone loss contributes to radiographic spinal progression in patients with axial spondyloarthritis.

OBJECTIVES: To investigate the longitudinal relationship between trabecular bone loss and spinal progression in axial spondyloarthritis (axSpA). METHODS: Patients enrolled in the Incheon Saint Mary's axSpA prospective observational cohort were evaluated. The number of syndesmophytes was assessed by two trained readers at baseline and at 2 and 4 years follow-up. Trabecular bone loss was assessed using the trabecular bone score (TBS). Disease activity measures included the BASDAI, ASDAS, CRP, and ESR. The relationship between trabecular bone loss and radiographic damage was investigated using generalized estimating equation models with 2 year time lags. RESULTS: Of the 245 patients included (80% males; mean (SD) age, 37 (12) years), 26 (11%) had mild trabecular bone loss (1.23-1.31) and 25 (10%) had severe trabecular bone loss (≤1.23) at baseline. Trabecular bone loss was associated with longitudinal radiographic spinal progression. Those with severe trabecular bone loss at baseline had an average 0.42 more syndesmophytes/2 years than those with normal TBS. Multivariate analysis revealed that severe trabecular bone loss compared with normal TBS resulted in an additional 0.4 syndesmophytes over 2 years. Adjusting for significant clinical factors revealed that both mild and severe trabecular bone loss were independent risk factors for new syndesmophyte formation over the next 2 years (OR [95% CI] = 2.4 [1.1-5.1]) and OR [95% CI] = 4.0 [1.6-9.7], respectively). CONCLUSIONS: Trabecular bone loss is longitudinally associated with spinal progression of axSpA. The more severe the trabecular bone loss, the stronger the effect on the progression of the spine.

Pulsed focused ultrasound treatment of muscle mitigates paralysis-induced bone loss in the adjacent bone: a study in a mouse model.

Bone loss can result from bed rest, space flight, spinal cord injury or age-related hormonal changes. Current bone loss mitigation techniques include pharmaceutical interventions, exercise, pulsed ultrasound targeted to bone and whole body vibration. In this study, we attempted to mitigate paralysis-induced bone loss by applying focused ultrasound to the midbelly of a paralyzed muscle. We employed a mouse model of disuse that uses onabotulinumtoxinA-induced paralysis, which causes rapid bone loss in 5 d. A focused 2 MHz transducer applied pulsed exposures with pulse repetition frequency mimicking that of motor neuron firing during walking (80 Hz), standing (20 Hz), or the standard pulsed ultrasound frequency used in fracture healing (1 kHz). Exposures were applied daily to calf muscle for 4 consecutive d. Trabecular bone changes were characterized using micro-computed tomography. Our results indicated that application of certain focused pulsed ultrasound parameters was able to mitigate some of the paralysis-induced bone loss.