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The influence of activity on calcium metabolism.

date: 12/01/1985
author: Whedon GD.
publication: J Nutr Sci Vitaminol (Tokyo). 1985 Dec;31 Suppl:S41-4.
pubmed_ID: 3915756
Many studies and observations have shown the bone-losing effects of physical inactivity of various forms. Contrariwise, less precise studies and observations have supported the reasonable premise that mechanical loading of the skeleton via physical activity shifts the balance of bone remodeling in favor of bone formation, and appears to do so at all ages. Some interesting starts have been made in research to discover the mechanisms of the action on bone of mechanical loading, but many pathways remain to be explored. Besides the mechanical forces, we need to know more about the interrelations of muscle function, probably mediated through muscle-tendon pull on periosteum, and more about other likely influences, notably changes in circulation to bones. The practical significance relative to calcium metabolism and aging of what has been learned thus far on the effects of activity, is that prolonged inactivity, either in a chair or in bed, is to be avoided, because of its deleterious effects, and that reasonably energetic gravitational exercise, such as walking or possibly jogging, promotes maintenance of bone health.

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Low magnitude mechanical loading is osteogenic in children with disabling conditions.

date: 03/19/2004
author: Ward K, Alsop C, Caulton J, Rubin C, Adams J, Mughal Z.
publication: J Bone Miner Res. 2004 Mar;19(3):360-9. Epub 2004 Jan 27.
pubmed_ID: 15040823

The osteogenic potential of short durations of low-level mechanical stimuli was examined in children with disabling conditions. The mean change in tibia vTBMD was +6.3% in the intervention group compared with -11.9% in the control group. This pilot randomized controlled trial provides preliminary evidence that low-level mechanical stimuli represent a noninvasive, non-pharmacological treatment of low BMD in children with disabling conditions. INTRODUCTION: Recent animal studies have demonstrated the anabolic potential of low-magnitude, high-frequency mechanical stimuli to the trabecular bone of weight-bearing regions of the skeleton. The main aim of this prospective, double-blind, randomized placebo-controlled pilot trial (RCT) was to examine whether these signals could effectively increase tibial and spinal volumetric trabecular BMD (vTBMD; mg/ml) in children with disabling conditions. MATERIALS AND METHODS: Twenty pre-or postpubertal disabled, ambulant, children (14 males, 6 females; mean age, 9.1 +/- 4.3 years; range, 4-19 years) were randomized to standing on active (n = 10; 0.3g, 90 Hz) or placebo (n = 10) devices for 10 minutes/day, 5 days/week for 6 months. The primary outcomes of the trial were proximal tibial and spinal (L2) vTBMD (mg/ml), measured using 3-D QCT. Posthoc analyses were performed to determine whether the treatment had an effect on diaphyseal cortical bone and muscle parameters. RESULTS AND CONCLUSIONS: Compliance was 44% (4.4 minutes per day), as determined by mean time on treatment (567.9 minutes) compared with expected time on treatment over the 6 months (1300 minutes). After 6 months, the mean change in proximal tibial vTBMD in children who stood on active devices was 6.27 mg/ml (+6.3%); in children who stood on placebo devices, vTBMD decreased by -9.45 mg/ml (-11.9%). Thus, the net benefit of treatment was +15.72 mg/ml (17.7%; p = 0.0033). In the spine, the net benefit of treatment, compared with placebo, was +6.72 mg/ml, (p = 0.14). Diaphyseal bone and muscle parameters did not show a response to treatment. The results of this pilot RCT have shown for the first time that low-magnitude, high-frequency mechanical stimuli are anabolic to trabecular bone in children, possibly by providing a surrogate for suppressed muscular activity in the disabled. Over the course of a longer treatment period, harnessing bone’s sensitivity to these stimuli may provide a non-pharmacological treatment for bone fragility in children.

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Pathological fractures in patients with cerebral palsy.

date: 10/01/1996
author: Brunner R, Doderlein L.
publication: J Pediatr Orthop B. 1996 Fall;5(4):232-8. Comment in: J Pediatr Orthop B. 1996 Fall;5(4):223-4.
pubmed_ID: 8897254

A retrospective study was made of 37 patients with 54 fractures that occurred without significant trauma. The morbidity and causes of these pathological fractures in patients with cerebral palsy were analyzed. The major causes for the fractures were long and fragile lever arms and stiffness in major joints, particularly the hips and knees. An additional factor was severe osteoporosis following a long period of postoperative immobilization. Seventy-four percent of the fractures occurred in the femoral shaft and supracondylar region. Stress fractures were rare (7%) and involved only the patella. Conservative treatment was sufficient in most cases but surgical fixation provided a good alternative for fractures of the femoral shaft. Intraarticular fractures with joint incongruity resulted in a decreased level of activity of the patient. Since osteoporosis is a major risk factor, patients with cerebral palsy should bear weight to prevent pathological fractures. Any stiffness of major joints and extended periods of immobilization should be avoided.

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Bone density and metabolism in children and adolescents with moderate to severe cerebral palsy.

date: 07/01/2002
author: Henderson RC, Lark RK, Gurka MJ, Worley G, Fung EB, Conaway M, Stallings VA, Stevenson RD.
publication: Pediatrics. 2002 Jul;110(1 Pt 1):e5.
pubmed_ID: 12093986

OBJECTIVES: Diminished bone density and a propensity to fracture with minimal trauma are common in children and adolescents with moderate to severe cerebral palsy (CP). The purpose of this study was to provide a detailed evaluation of bone mineral density (BMD) and metabolism in this population and to assess the relationship of these measures to multiple other clinical, growth, and nutrition variables. METHODS: The study group consisted of 117 subjects ages 2 to 19 years (mean: 9.7 years) with moderate to severe CP as defined by the Gross Motor Functional Classification scale. Population-based sampling was used to recruit 62 of the participants, which allows for estimations of prevalence. The remaining 55 subjects were a convenience sampling from both hospital- and school-based sources. The evaluation included measures of BMD, a detailed anthropometric assessment of growth and nutritional status, medical and surgical history, the Child Health Status Questionnaire, and multiple serum analyses. BMD was measured in the distal femur, a site specifically developed for use in this contracted population, and the lumbar spine. BMD measures were converted to age and gender normalized z scores based on our own previously published control series (n > 250). RESULTS: Osteopenia (BMD z score <-2.0) was found in the femur of 77% of the population-based cohort and in 97% of all study participants who were unable to stand and were older than 9 years. BMD was not as low in the lumbar spine (population-based cohort mean +/- standard error z score: -1.8 +/- 0.1) as in the distal femur (mean z score: -3.1 +/- 0.2). Fractures had occurred in 26% of the children who were older than 10 years. Multiple clinical and nutritional variables correlated with BMD z scores, but interpretation of these findings is complicated by covariance among variables. In stepwise regression analyses, it was found that severity of neurologic impairment as graded by Gross Motor Functional Classification level, increasing difficulty feeding the child, use of anticonvulsants, and lower triceps skinfold z scores (in decreasing order of importance) all independently contribute to lower BMD z scores in the femur. CONCLUSIONS: Low BMD is prevalent in children with moderate to severe CP and is associated with significant fracture risk. The underlying pathophysiology is complex, with multiple factors contributing to the problem and significant variation between different regions of the skeleton.

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Modulation of bone loss during calcium insufficiency by controlled dynamic loading.

date: 04/01/1986
author: Lanyon LE, Rubin CT, Baust G.
publication: Calcif Tissue Int. 1986 Apr;38(4):209-16.
pubmed_ID: 3085898

Changes in the midshaft cross-sectional area of the ulna were measured in egg-laying turkeys on a diet insufficient in calcium. Left:right comparisons were used to assess the bone loss over a six-week period due to 1) calcium insufficiency, 2) calcium insufficiency plus disuse, and 3) calcium insufficiency and disuse interrupted by a short daily period of intermittent loading applied from an external device. Calcium insufficiency alone in the intact ulna resulted in a 15% reduction in cross-sectional area. In the functionally deprived bones this loss was increased to 32%. In bones where the disuse was interrupted by a single short daily period of loading, the degree of bone loss was significantly modified (P less than 0.006) to 25%. No significant difference in the modulating effect of loading was achieved by varying the peak strain from 0.0015 to 0.003, the strain rate from 0.01 to 0.05, or the duration of the single loading period from 100 sec per day to 25 minutes. All the loading regimes employed had been demonstrated to be osteogenic in mature male birds on a diet sufficient in calcium.

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Static vs dynamic loads as an influence on bone remodeling.

date: 01/01/2004
author: Lanyon LE, Rubin CT.
publication: J Biomech. 1984;17(12):897-905.
pubmed_ID: 6520138

Remodeling activity in the avian ulna was assessed under conditions of disuse alone, disuse with a superimposed continuous compressive load, and disuse interrupted by a short daily period of intermittent loading. The ulnar preparation consisted of the 110mm section of the bone shaft between two submetaphyseal osteotomies. Each end of the preparation was transfixed by a stainless steel pin and the shaft either protected from normal functional loading with the pins joined by external fixators, loaded continuously in compression by joining the pins with springs, or loaded intermittently in compression for a single 100s period per day by engaging the pins in an Instron machine. Similar loads (525 N) were used in both static and dynamic cases. The strains engendered were determined by strain gauges, and at their maximum around the bone’s midshaft were -0.002. The intermittent load was applied at a frequency of 1 Hz as a ramped square wave, with a rate of change of strain during the ramp of 0.01 s-1. Peak strain at the midshaft of the ulna during wing flapping in the intact bone was recorded from bone bonded strain gauges in vivo as -0.0033 with a maximum rate of change of strain of 0.056 s-1. Examination of bone sections from the midpoint of the preparation after an 8 week period indicated that in both non-loaded and statically loaded bones there was an increase in both endosteal diameter and intra cortical porosity. These changes produced a decrease in cross sectional area which was similar in the two groups (-13%).(ABSTRACT TRUNCATED AT 250 WORDS)

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Can Using Standers Increase Bone Density In Non-Ambulatory Children?

date: 10/01/2006
author: Katz, Danielle,MD, Snyder, Bryan MD, PhD, Dodek, Anton MD, Holm, Ingrid MD Miller, Claire BS
publication: Abstract as published in the American Academy of Cerebral Palsy and Developmental Medicine (AACPDM) 2006 Conference Proceedings

Purpose: Pathologic fractures are a significant source of morbidity for non-ambulatory children with neuromuscular dysfunction. We hypothesize that increasing weight-bearing in non-ambulatory children will increase bone material density (BMD) and decrease fracture risk. The aim of this pilot study was to demonstrate that non-ambulatory children participating in a standing program for at least two hours a day will experience an increase in BMD in the weight bearing bones. We also evaluate the reliability of measuring BMD at the calcaneous (weight bearing bones) and distal forearm (non-weight bearing bone) using peripheral DXA in delayed, non-ambulatory children.

Methods: After receiving IRB approval, 12 non-ambulatory, quadriplegic children (ages 12-21) consented to participate in a 2 hour/day, 5 day/week standing program. A history, orthopaedic exam, determination of bone age, laboratory tests for metabolic bone disease and BMD at the calcaneal tuberosity and distal forearm metaphyses were obtained. Compliance with the prescribed standing program was monitored for 6 months. BMD was measured using peripheral DXA at baseline and every 3 months. Using Jan. 2003 BMD data as a baseline, the ratio of change in BMD at the calcaneous and distal forearm was evaluated as a function of percent compliance with standing program.

Results: Intrarater reliability for BMD measured by peripheral DXA was good: Pearson correlation for the calcaneous = 0.90 (p=0.01) and for the forearm = 0.96 (p=0.01). Paired t test between two sets of data measured at each site on the same day were not different for calcaneous (t=0.92, df=15, p=0.37) or forearm (t=0.05, df=15, p=0.96). Compliance with the standing program was inconsistent. No patients were 100% compliant. Patients tended to stand longer at the initiation of the study Jan.-April (Jan vs Apr, p = 0.018; Jan vs Jul, p = 0.89; Apr vs Jul, p = 0.063). Compliance (%) was positively correlated (r = -0.62) with increased calcaneous BMD measured in April. This is in contrast to forearm BMD measured at the same time; which was negatively correlated (r = -0.44) with standing compliance. This support the notion that standing preferentially increases bone mass in the weight-bearing bones. However the BMD at the calcaneous measured in July was decreased, perhaps reflecting the decreased compliance the with standing program over the succeeding interval April-July.

Conclusion: It is feasible to have non-ambulatory children participate in a rigorous standing program. The weight bearing ?dose? affects BMD at the calcaneous but the benefit appears to be transient if the intensive standing program is not sustained.

Significance: The intensive use of standers (10 hours/wk) may have a beneficial effect on BMD of weight bearing bones in non-ambulatory children.

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Bone measurements by peripheral quantitative computed tomography (pQCT) in children with cerebral palsy

date: 12/01/2005
author: Binkley T, Johnson J, Vogel L, Kecskemethy H, Henderson R, Specker B.
publication: J Pediatr. 2005 Dec;147(6):791-6.
pubmed_ID: 16356433

OBJECTIVE: To use peripheral quantitative computed tomography (pQCT) to determine bone measurements in patients with cerebral palsy (CP) age 3 to 20 years and compare them with control subjects. STUDY DESIGN: A total of 13 (5 male) patients with CP, along with 2 sex- and age-matched controls for each, were included in a mixed-model analysis with matched pairs as random effects for pQCT bone measurements of the 20% distal tibia. RESULTS: Tibia length was similar in the CP and control groups (P = .57). Weight was marginally higher in the control group (P = .06). Cortical bone mineral content (BMC), area, thickness, polar strength-strain index (pSSI), and periosteal and endosteal circumferences were greater in the control group (P < .05 for all). Relationships between bone measurements and weight showed that cortical BMC, area, periosteal circumference, and pSSI were greater at higher weights in the control group (group-by-weight interaction, P < .05 for all). Cortical thickness was greater in the control group and was correlated with weight. Cortical volumetric bone mineral density (vBMD) was greater with higher weights in the CP group (group-by-weight interaction, P = .03). CONCLUSIONS: Bone strength, as indicated by pSSI, is compromised in children with CP due to smaller and thinner bones, not due to lower cortical bone density.

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Longitudinal changes in bone density in children and adolescents with moderate to severe cerebral palsy.

date: 06/01/2005
author: Henderson RC, Kairalla JA, Barrington JW, Abbas A, Stevenson RD.
publication: J Pediatr. 2005 Jun;146(6):769-75
pubmed_ID: 15973316

OBJECTIVE: To assess the natural history of “growth” in bone mineral density (BMD) in children and adolescents with moderate to severe cerebral palsy (CP). STUDY DESIGN: A prospective, longitudinal, observational study of BMD in 69 subjects with moderate to severe spastic CP ages 2.0 to 17.7 years. Fifty-five subjects were observed for more than 2 years and 40 subjects for more than 3 years. Each evaluation also included assessments of growth, nutritional status, Tanner stage, general health, and various clinical features of CP. RESULTS: Lower BMD z-scores at the initial evaluation were associated with greater severity of CP as judged by gross motor function and feeding difficulty, and with poorer growth and nutrition as judged by weight z-scores. BMD increased an average of 2% to 5%/y in the distal femur and lumbar spine, but ranged widely from +42%/y to -31%. In spite of increases in BMD, distal femur BMD z-scores decrease with age in this population. CONCLUSIONS: Children with severe CP develop over the course of their lives clinically significant osteopenia. Unlike elderly adults, this is not primarily from true losses in bone mineral, but from a rate of growth in bone mineral that is diminished relative to healthy children. The efficacy of interventions to increase BMD can truly be assessed only with a clear understanding of the expected changes in BMD without intervention.

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Bone mineral density in children with cerebral palsy.

date: 04/01/2001
author: Tasdemir HA, Buyukavci M, Akcay F, Polat P, Yildiran A, Karakelleoglu C.
publication: Pediatr Int. 2001 Apr;43(2):157-60.
pubmed_ID: 11285068

BACKGROUND: The purpose of the present study was to evaluate the severity of and factors related to osteopenia in children with cerebral palsy (CP). METHODS: Bone mineral density (BMD), calcium (Ca), phosphate (P), alkaline phosphatase (ALP), creatinine, parathyroid hormone (PTH) and 25-hydroxy vitamin D3 (25OHD3) concentrations were determined in 24 children with CP (15 ambulant, nine non-ambulant), aged between 10 months and 12 years (mean (+/-SD) 4.1+/-2.9 years). These vaules were compared with data obtained from a control group. RESULTS: Adjusted mean BMD values were lower in the patient group than in controls (P<0.05). However, there was no difference between BMD values of ambulant and non-ambulant patients. The Ca and P levels of the patient group were significantly higher than those of controls (P<0.05). CONCLUSIONS: The present study showed that BMD was decreased in all children with CP, but to a greater extent in non-ambulant children with CP, and immobilization is the major effective factor on bone mineralization.