Ralf Beccard

Reshaping of Vertebrae during Treatment with Neridronate or Pamidronate in Children with Osteogenesis Imperfecta

Background/Aims: Osteogenesis imperfecta (OI) is a hereditary disease causing increased bone fragility. Pamidronate (PAM), which has to be administered as a 3-day course according to the original protocol by Glorieux, is the most frequently used therapy. Other bisphosphonates like neridronate (NER), which can be infused during an outpatient visit, have also proven to be effective. This is the first analysis comparing the effect of PAM and NER using vertebral morphometry. Methods: 28 patients with OI type III and IV were retrospectively analyzed by matched pairs. Results: No differences were detected between patients treated with PAM or NER at the start of therapy: mean age 4.4 years (p = 0.730), mean height 86.8 cm/85.3 cm (p = 0.854), lumbar vertebral area 208.9 mm2/206.0 mm2 (p = 0.555), and in all vertebral indices. After 1 year of treatment (mean 1.16 years; p = 0.854) both groups showed a significant increase in the vertebral area and improved vertebral indices. Again there were no differences between the groups in the vertebral area (p = 0.590). Conclusion: In this study there was no difference between patients treated with PAM or NER regarding vertebral morphometry during the first year of therapy. Because of the possibility of an outpatient setting, NER is convenient for these children.

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.

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.

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.

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 (R2adjusted = 0.960) and females (R2adjusted = 0.934). Height was a stronger predictor of FL than Tanner stages. Compared to controls, patients with OI were characterized by lower BMC-SDSFL and lower BMC-SDSheight (–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-SDSFL was not significantly lower than BMC-SDSheight 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.

THE INFLUENCE OF WHOLE-BODY VIBRATION AND IGF-I ON MUSCLE PARALYSIS-INDUCED BONE DEGRADATION

Mechanical loading through muscle contraction is essential for bone homeostasis and maintenance. Consequently, muscle paralysis induced by Botulinum neurotoxin (Botox) results in bone degradation [Warner, 2006]. On the other hand, it is well known that high-frequency mechanical loading has an anabolic effect on bone (Rubin et al. 2004) and that insulin growth factor I (IGF-I) is essential for bone growth and formation [Baker, 1993]. Interestingly, it has been shown that skeletal unloading leads to a resistance to IGF-I [Bikle, 1994, Sakata, 2004]. The purpose of the present study was to analyze if whole body vibration (WBV) and IGF-I can counteract muscle paralysisinduced bone degradation.

Einflussfaktoren auf die Entwicklung des Skeletts

ZusammenfassungMuskeln und Knochen sind ein funktionelles System, das sich immer wieder den neuen Gegebenheiten anpasst. Der Aufbau der Knochenmasse erfolgt im Kindes- und Jugendalter. Körperliche Aktivität und gesunde Ernährung sind dafür wichtige Voraussetzungen.