Effect of whole-body vibration and insulin-like growth factor-I on muscle paralysis-induced bone degeneration after botulinum toxin injection in mice.

Botulinum toxin A (BTX)-induced muscle paralysis results in pronounced bone degradation with substantial bone loss. We hypothesized that whole-body vibration (WBV) and insulin-like growth factor-I (IGF-I) treatment can counteract paralysis-induced bone degradation following BTX injections by activation of the protein kinase B (Akt) signaling pathway. Female C57BL/6 mice (n = 60, 16 weeks) were assigned into six groups (n = 10 each): SHAM, BTX, BTX+WBV, BTX+IGF-I, BTX+WBV+IGF-I, and a baseline group, which was killed at the beginning of the study. Mice received a BTX (1.0 U/0.1 mL) or saline (SHAM) injection in the right hind limb. The BTX+IGF-I and BTX+WBV+IGF-I groups obtained daily subcutaneous injections of human IGF-I (1 µg/day). The BTX+WBV and BTX+WBV+IGF-I groups underwent WBV (25 Hz, 2.1 g, 0.83 mm) for 30 min/day, 5 days/week for 4 weeks. Femora were scanned by pQCT, and mechanical properties were determined. On tibial sections TRAP staining, static histomorphometry, and immunohistochemical staining against Akt, phospho-Akt, IGF-IR (IGF-I receptor), and phospho-IGF-IR were conducted. BTX injection decreased trabecular and cortical bone mineral density. The WBV and WBV+IGF-I groups showed no difference in trabecular bone mineral density compared to the SHAM group. The phospho-IGF-IR and phospho-Akt stainings were not differentially altered in the injected hind limbs between groups. We found that high-frequency, low-magnitude WBV can counteract paralysis-induced bone loss following BTX injections, while we could not detect any effect of treatment with IGF-I.

Analyses of muscular mass and function: the impact on bone mineral density and peak muscle mass.

Bone density and bone mass are commonly regarded as the essential parameters to describe fracture risk in osteology. Because fractures primarily depend on bone strength and secondarily on bone mass and density, bone strength should be the main parameter to describe fracture risk. The quantitative description of bone strength has the prerequisite that bone geometry is assessed despite bone density. Thus, volumetric osteodensitometric methods should be preferred, which enable the physician to evaluate parameters primarily associated with bone modeling or remodeling. Modeling describes the adaptation of bone geometry to applied muscular forces in contrast to remodeling representing bone turnover. The adaptation of bone geometry to muscle forces led to the term functional muscle-bone unit, which enables the physician to differentiate between primary and secondary bone diseases. Primary bone diseases are characterized by a defective adaptation of bone to muscle forces in contrast to secondary bone diseases, which are primary diseases of the neuromuscular system. Because muscle forces are essential in the feedback loop of bone adaptation to forces (mechanostat), the assessment of muscle function has become an essential part of osteologic diagnostics in pediatrics. Dynamometric and mechanographic methods have been introduced to properly characterize kinetic aspects of muscle function in children and adolescents. Therefore, emphasis should be put on the assessment of muscle function despite the evaluation of osteodensitometric parameters in pediatric osteology.

The relationship between body composition and the urinary excretion of deoxypyridinoline and galactosyl-hydroxylysine in children and adolescents.

The study intends to investigate the relationship of body composition (%fat, percent body fat; FM, fat mass; FFM, fat free mass; FA and MA cross-sectional fat and muscle area) to the urinary excretion of deoxypyridinoline (DPD) and galactosyl-hydroxylysine (Gal-Hyl). 231 healthy children and adolescents (age 5-19 years; 112 males) of the DONALD study were analyzed for FM and FFM by measuring 4 skinfold thicknesses, for DPD and Gal-Hyl in urine samples and for bone parameters, FA and MA at the forearm by peripheral quantitative computed tomography. In contrast to adrenarchal females, adrenarchal males with low %fat had low levels of DPD and Gal-Hyl. %fat was correlated with DPD in pre-adrenarchal males (r = 0.290) and females (r = 0.298). Cortical bone mineral density (BMDcort) was correlated with DPD (r = -0.351) in adrenarchal males. Controlled for BMDcort, FM was correlated with DPD in pre-adrenarchal males (r = 0.348), and FA was correlated with DPD in pre-adrenarchal females (r = 0.294). FFM was negatively correlated with Gal-Hyl in adrenarchal males (r = -0.436) and females (r = -0.338). Less than 40% of variance of excreted DPD and Gal-Hyl was explained by regression models based on parameters of body composition. The effect of body composition explains the minor part of variance of the urinary excretion of DPD and Gal-Hyl. The association of body composition to excreted DPD and Gal-Hyl was not explained by the effect of adipose tissue on bone formation and bone resorption.

Forearm length - a new tool to standardize bone parameters of the forearm measured with peripheral quantitative computed tomography in individuals with disproportional growth of forearm length and body height.

AIM: To investigate the relationship of forearm length (FL) or height to bone parameters of the forearm of a normal pediatric population in comparison to individuals with osteogenesis imperfecta (OI). METHODS: Data on FL, height and peripheral quantitative computed tomography measurements of the forearm were collected from participants of the DONALD study (140 males and 156 females; age 5-19 years) and from 73 patients with OI (53 males; mean age +/- SD: 11.7 +/- 3.3 years). Bone mineral content (BMC) was transformed into standard deviation score (SDS) according to height or FL. RESULTS: Height and Tanner stages significantly predicted FL in males (R(2)(adjusted) = 0.960) and females (R(2)(adjusted) = 0.934). Height was a stronger predictor of FL than Tanner stages. Compared to controls, patients with OI were characterized by lower BMC-SDS(FL) and lower BMC-SDS(height) (-0.37 +/- 1.77 vs. 0.00 +/- 0.97, p = 0.002, and -0.15 +/- 5.0 vs. -0.02 +/- 1.01, p = 0.011, respectively). BMC-SDS(FL) was not significantly lower than BMC-SDS(height) in controls, and also not lower in patients with OI (p = 0.865 and p = 0.809). The height/FL ratio was significantly decreased in patients with OI (mean +/- SD: 6.34 +/- 0.38 vs. 6.45 +/- 0.21, p = 0.001) compared with controls. CONCLUSION: Because of disproportional growth, BMC may be overestimated in OI patients.

The 'functional muscle-cartilage unit': a reasonable approach to describe a putative relationship between muscle force and longitudinal growth at the forearm in children and adolescents?

BACKGROUND: Several reports give evidence that the perichondral ossificiation of bone tubes (modeling) strongly depends on muscular forces in children and adolescents. The present analyses intend to investigate the hypothesis that muscular forces also partly determine enchondral ossification and, therefore, longitudinal growth of bone tubes. SUBJECTS AND METHODS: Analyses were based on a single cross-sectional investigation with peripheral quantitative computed tomography in 296 individuals (age 5-19 years) participating in the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study. RESULTS: Forearm length (FL) was correlated with body height in gender-related subgroups of prepubertal and pubertal individuals (rs between 0.76 and 0.86). Cross-sectional muscle area (MA) increased faster than FL and faster than cross-sectional bone area (BA) close to the distal growth plate in puberty. Close to the growth plate, longitudinal growth was faster than perichondral ossification in females. The ratio MA/BA (surrogate of pressure on the distal growth plate) was correlated with FL in prepubertal boys (r = -0.249, p = 0.043) and pubertal individuals (r = 0.153, p = 0.051). CONCLUSIONS: Results support the hypothesis that longitudinal growth precedes modeling at the distal forearm. Confounding variables such as puberty may modify the relationship between muscle forces and longitudinal growth at the forearm in boys.

Oscillatory whole-body vibration improves exercise capacity and physical performance in pulmonary arterial hypertension: a randomised clinical study.

OBJECTIVE: In patients with pulmonary arterial hypertension (PAH), supportive therapies may be beneficial in addition to targeted medical treatment. Here, we evaluated the effectiveness and safety of oscillatory whole-body vibration (WBV) in patients on stable PAH therapy. METHODS: Twenty-two patients with PAH (mean PAP≥25 mm Hg and pulmonary arterial wedge pressure (PAWP)≤15 mm Hg) who were in world health organization (WHO)-Functional Class II or III and on stable PAH therapy for≥3 months, were randomised to receive WBV (16 sessions of 1-hour duration within 4 weeks) or to a control group, that subsequently received WBV. Follow-up measures included the 6-min walking distance (6MWD), cardiopulmonary exercise testing (CPET), echocardiography, muscle-power, and health-related quality of life (HRQoL; SF-36 and LPH questionnaires). RESULTS: When compared to the control group, patients receiving WBV exhibited a significant improvement in the primary endpoint, the 6MWD (+35.4±10.9 vs -4.4±7.6 m), resulting in a net benefit of 39.7±7.8 m (p=0.004). WBV was also associated with substantial improvements in CPET variables, muscle power, and HRQoL. The combined analysis of all patients (n=22) indicated significant net improvements versus baseline in the 6MWD (+38.6 m), peakVO2 (+65.7 mL/min), anaerobic threshold (+40.9 mL VO2/min), muscle power (+4.4%), and HRQoL (SF-36 +9.7, LPH -11.5 points) (all p<0.05). WBV was well tolerated in all patients, and no procedure-related severe adverse events (SAEs) occurred. CONCLUSIONS: WBV substantially improves exercise capacity, physical performance, and HRQoL in patients with PAH who are on stable targeted therapy. This methodology may be utilised in structured training programmes, and may be feasible for continuous long-term physical exercise in these patients. TRIAL REGISTRATION NUMBER: NCT01763112; Results.

N-terminal C-type natriuretic propeptide is associated with the endosteal apposition of bone in females with a persistent eating disorder.

BACKGROUND/AIM: Females with anorexia nervosa (AN) are often affected by osteoporosis. The study intends to investigate the association between serum levels of the N-terminal propeptide of the C-type natriuretic peptide (NT-proCNP) and bone development in anorexic females. SUBJECTS AND METHODS: In a catamnestic visit, 21 females, formerly treated for AN, were assessed for the presence of eating disorders and analyzed for bone parameters of the distal radius (4% site) with peripheral quantitative computed tomography (pQCT), for maximal isometric grip force (MIGF) and for NT-proCNP serum levels. RESULTS: The 9 females with a persistent eating disorder had lower height and weight than the recovered girls. NT-proCNP was correlated with the cortical area (r = 0.521), the endosteal circumference (CE, r = -0.468) and the ratio of MIGF to cross-sectional bone area (r = 0.434). CE explained 40% of the variance of NT-proCNP in females with persistent eating disorders, but was not associated with NT-proCNP in recovered girls (p = 0.691). The association between CE and NT-proCNP was not existent when the correlation was controlled for the duration of amenorrhea and the supplemented cumulative dose of ethinylestradiol (p = 0.275). CONCLUSION: NT-proCNP reflects metaphyseal inwaisting which is modified by estrogens and the pressure on the growth plate.

Do bone mineral density, bone geometry and the functional muscle-bone unit explain bone fractures in healthy children and adolescents?

BACKGROUND/AIMS: Because the increasing fracture incidence has not been understood, the present study compares variables of the muscle-bone interaction to examine the hypothesis that an impaired adaptation of bone strength to muscle forces explains this phenomenon. METHODS: The forearm of 220 individuals (mean age 11.1 ± 3.2 years; range 5.5-17.4 years) was analyzed by peripheral quantitative computed tomography. Bone mineral content (BMC), bone mineral density, periosteal circumference, cortical area, strength strain index (SSI) and muscle area (MA) were measured at the distal and proximal radius of the non-dominant forearm. Maximum isometric grip force was measured by a dynamometer. The fracture history was evaluated by a questionnaire after a period of 5 ± 1.7 years. RESULTS: During the observational period at least one fracture appeared in 78 children and adolescents (35.5%). Individuals with and without fractures were not different in age, height, weight, and body mass index. Variables of bone mineral density, bone geometry and muscle force were not different between both groups. BMC, MA and SSI were dependent on age and sex. CONCLUSION: Fracture risk in healthy children and adolescents is not sufficiently explained by volumetric bone mineral density, the skeletal phenotype and indices of the functional muscle-bone unit.