Spinal Cord Injury as a Model of Bone-Muscle Interactions: Therapeutic Implications From in vitro and in vivo Studies

The aim of this systematic review was to determine if eccentric exercise is superior to concentric exercise in stimulating gains in muscle strength and mass. Meta-analyses were performed for comparisons between eccentric and concentric training as means to improve muscle strength and mass. In order to determine the importance of different parameters of training, subgroup analyses of intensity of exercise, velocity of movement and mode of contraction were also performed. Twenty randomised controlled trials studies met the inclusion criteria. Meta-analyses showed that when eccentric exercise was performed at higher intensities compared with concentric training, total strength and eccentric strength increased more significantly. However, compared with concentric training, strength gains after eccentric training appeared more specific in terms of velocity and mode of contraction. Eccentric training performed at high intensities was shown to be more effective in promoting increases in muscle mass measured as muscle girth. In addition, eccentric training also showed a trend towards increased muscle cross-sectional area measured with magnetic resonance imaging or computerised tomography. Subgroup analyses suggest that the superiority of eccentric training to increase muscle strength and mass appears to be related to the higher loads developed during eccentric contractions. The specialised neural pattern of eccentric actions possibly explains the high specificity of strength gains after eccentric training. Further research is required to investigate the underlying mechanisms of this specificity and its functional significance in terms of transferability of strength gains to more complex human movements.

Since the use of parathyroid hormone as a treatment for osteoporosis is limited to two years or less, the question of whether antiresorptive therapy should follow parathyroid hormone therapy is important. We previously reported results after the first year of this randomized trial comparing the use of full-length parathyroid hormone (1-84) alone, alendronate alone, or both combined. In the continuation of this trial, we asked whether antiresorptive therapy is required to maintain gains in bone mineral density after one year of therapy with parathyroid hormone (1-84). In the data reported here, women who had received parathyroid hormone (1-84) monotherapy (100 microg daily) in year 1 were randomly reassigned to one additional year with either placebo (60 subjects) or alendronate (59 subjects). Subjects who had received combination therapy in year 1 received alendronate in year 2; those who had received alendronate monotherapy in year 1 continued with alendronate in year 2. Bone mineral density at the spine and hip was assessed with the use of dual-energy x-ray absorptiometry and quantitative computed tomography (CT). Over two years, alendronate therapy after parathyroid hormone therapy led to significant increases in bone mineral density in comparison with the results for placebo after parathyroid hormone therapy, a difference particularly evident for bone mineral density in trabecular bone at the spine on quantitative CT (an increase of 31 percent in the parathyroid hormone-alendronate group as compared with 14 percent in the parathyroid hormone-placebo group). During year 2, subjects receiving placebo lost substantial bone mineral density. After one year of parathyroid hormone (1-84), densitometric gains appear to be maintained or increased with alendronate but lost if parathyroid hormone is not followed by an antiresorptive agent. These results have clinical implications for therapeutic choices after the discontinuation of parathyroid hormone. Copyright 2005 Massachusetts Medical Society.

A novel concept of "gasotransmitter" arrived recently. Gasotransmitters are small molecules of endogenous gases with important physiological functions. Their production and metabolism are enzymatically regulated, and their effects are not dependent on specific membrane receptors. Following the identification of nitric oxide and carbon monoxide as gasotransmitters, hydrogen sulfide (H(2)S) may be qualified as the third gasotransmitter. Recent studies have shown that H(2)S is generated from vascular smooth muscle cells (SMCs), catalyzed by specific H(2)S-generating enzyme. At physiologically relevant concentrations, H(2)S relaxes vascular tissues, an effect mediated by the activation of ATP-sensitive K(+) (K(ATP)) channels in vascular SMCs. H(2)S directly alters the activity of K(ATP) channels without the involvement of second messengers. Furthermore, the endogenous production of H(2)S in the cardiovascular system is likely regulated by nitric oxide, whereas the vasorelaxant effect of nitric oxide is inhibited by H(2)S. It is anticipated that future studies will better reveal the molecular mechanisms underlying the effect of H(2)S on K(ATP) channel proteins, the interaction of H(2)S and other gasotransmitters in cardiovascular system, the endogenous stimulators and inhibitors of H(2)S metabolism, the role of H(2)S in the regulation of heart function, and the abnormal H(2)S production and action under various pathophysiological conditions.