Distal Femur Bone Mineral Density Research Articles

Intraoperative physician assessment of bone: correlation to bone mineral density.

Intuitively, intraoperative physician assessment (IPA) would be an excellent measure of bone status gained through haptic feedback during bone preparation. However, no studies have evaluated the orthopedic surgeon's ability to do so. This study's purpose, in patients undergoing total knee arthroplasty (TKA), was to relate IPA with (1) the lowest bone mineral density (BMD) T-score at routine clinical sites; and (2) with distal femur BMD. Seventy patients undergoing TKA by 3 surgeons received pre-operative DXA. Intraoperatively, bone quality was assessed on a 5-point scale (1 excellent to 5 poor) based on tactile feedback to preparation. Demographic data, DXA results, and IPA score between surgeons were compared by factorial ANOVA. Lowest T-score and distal femur BMD were associated with IPA using Spearman's correlation. The mean (SD) age and BMI were 65.8 (7.6) years and 31.4 (5.1) kg/m2, respectively. Patient demographic data, BMD, and IPA (mean [SD] = 2.74 [1.2]) did not differ between surgeons. IPA correlated with the lowest T-score (R = 0.511) and distal femur BMD (R = 0.603-0.661). Based on the lowest T-score, no osteoporotic patients had an IPA above average, and none with normal BMD was classified as having poor bone. IPA is highly correlated with local (distal femur) and overall BMD. This study supports the International Society for Clinical Densitometry position that surgeon concern regarding bone quality should lead to bone health assessment. As IPA is comparable between surgeons, it is logical this can be widely applied by experienced orthopedic surgeons. Future studies evaluating IPA at other anatomic sites are indicated.

Denervation impacts muscle quality and knee bone mineral density after spinal cord injury

Cross-sectional study. To compare muscle size, body composition, bone mineral density (BMD), and metabolic profiles in denervated versus innervated individuals with spinal cord injury (SCI). Hunter Holmes McGuire Veterans Affairs (VA) Medical Center. Body composition, bone mineral density (BMD), muscle size, and metabolic parameters were collected in 16 persons with chronic SCI (n = 8 denervated, n = 8 innervated) using dual-energy x-ray absorptiometry (DXA), magnetic resonance imaging (MRI), and fasting blood samples. BMR was measured by indirect calorimetry. Percent differences of the whole thigh muscle cross-sectional area (CSA; 38%), knee extensor CSA (49%), vasti CSA (49%), and rectus femoris CSA (61%) were smaller in the denervated group (p < 0.05). Leg lean mass was also lower (28%) in the denervated group (p < 0.05). Whole muscle intramuscular fat (IMF%; 15.5%), knee extensor IMF% (22%), and % fat mass (10.9%) were significantly greater in the denervated group (p < 0.05). Knee distal femur and proximal tibia BMD were lower in the denervated group, 18-22% and 17-23%; p < 0.05. Certain indices of metabolic profile were more favorable in the denervated group though were not significant. SCI results in skeletal muscle atrophy and dramatic changes in body composition. Lower motor neuron (LMN) injury results in denervation of the lower extremity muscles which exacerbates atrophy. Denervated participants exhibited lower leg lean mass and muscle CSA, greater muscle IMF, and reduced knee BMD compared to innervated participants. Future research is needed to explore therapeutic treatments for the denervated muscles after SCI.

Bisphosphonates Alleviate Bone Loss in People with Acute Spinal Cord Injury：A Systematic Review and Meta-Analysis

Bone loss is not to be underestimated in people with acute spinal cord injury (SCI). Bisphosphonates can inhibit the bone resorption of osteoclast. To study whether the early application of bisphosphonates can alleviate bone loss after acute SCI, we included 7 randomized controlled trials for meta-analysis. Seven randomized controlled trials were found in literature databases. The percentage change in bone mineral density (BMD) at different sites were primary outcomes and serum bone turnover markers were secondary outcomes. A random-effects model was selected for meta-analysis. There were significant differences in the percentage change in BMD of the lumbar spine, total hip, and femoral neck between the bisphosphonates and control groups, but not in the percentage change in distal femur BMD. Besides, there were no statistically significant differences between the groups in the bone formation marker Procollagen type 1N propeptide; bisphosphonates were effective in reducing the C-terminal telopeptide at the 6-month follow-up, but not at the 12-month follow-up. Subgroup analysis of the effects of zoledronate showed positive effects on BMD of the lumbar spine, total hip, and femoral neck at the 6-month follow-up and showed positive effects on BMD of the total hip and femoral neck at the 12-month follow-up. Bisphosphonates can effectively alleviate the bone loss of the lumbar spine, total hip, and femoral neck in patients with acute SCI, and early application is advocated.

Cross-Sectional Study of Knee Bone Mineral Density and Fragility Fractures in Patients with Neurological Injuries and Neuromuscular Disorders

Background: Patients with neurological injury and neuromuscular disorders are at increased risk for osteoporosis and fragility fracture. This cross-sectional study investigated whether knee bone mineral density (BMD) correlates with fragility fracture in patients with neurological injury and neuromuscular injuries. Methodology: In this retrospective chart review, 435 participants underwent dual-energy X–ray absorptiometry (DXA) for BMD analysis. Distal femur and proximal tibial BMD measurements were performed as per the Toronto protocol. Spine, hip, and forearm DXA was performed following the standards of the International Society of Clinical Densitometry, 2019. Blinded and independent clinical evaluations and laboratory exams were performed. Participants were divided into groups with and without fracture confirmed by clinical history and radiography. Results: Distal femur and proximal tibial BMD were measured in 288/435 (66.2%) participants. Osteoporosis was noted in 138/288 (47.9%) patients. Fractures occurred in 95/435 participants (21.8%), including one fracture in 64/435 participants (14.7%), two fractures in 24/435 participants (5.5%), and greater than two fractures in 7/435 patients (1.6%). Fractures were noted in 23/54 (42.6%) participants with post-polio syndrome, 21/66 with brain injury (31.8%), 3/10 (30%) with brain injury and spinal cord injury, 24/98 (24.5%) with neuromuscular disorders, 9/52 (17.3%) with nontraumatic spinal cord injury, and 15/155 (9.7%) with traumatic spinal cord injury. The median BMD of the knee and hip was lower in participants with fractures. Distal femur and proximal tibial BMD (odds ratio [OR] = 0.02, 95% confidence interval [CI]: 0.01–0.45) remained independently associated with fragility fracture in multivariable analysis. Conclusion: Proximal tibial and distal femur BMD measurements offered additional information on neurological injury and neuromuscular disorders.

Effect of Low Dietary Vitamin D Fed Prior to and During Pregnancy and Lactation on Maternal Bone Mineral Density, Structure, and Strength in C57BL/6 Mice.

ABSTRACTSeveral studies have shown that diets containing lower vitamin D than in the AIN-93G diet do not compromise bone structure, bone mineral density (BMD), and/or bone strength in male and female mice. This study determined if a diet containing low vitamin D from prepregnancy through to the end of lactation maintained these bone outcomes to a similar extent as a high vitamin D diet. Mice were fed an AIN-93G diet with 25 (LD diet) or 5000 (HD diet) IU vitamin D/kg diet from premating through to lactation (n = 15/group). Of the major structure outcomes, only cortical area fraction of the distal femur was lower (P <0.05) with the LD diet. Lumbar vertebra BMD was lower (P <0.05) with LD whereas distal femur BMD and bone strength at 3 sites did not differ. Dams fed an LD diet premating through to the end of lactation had largely similar bone outcomes to dams fed a HD diet.

Bone Mineral Density at the Distal Femur and Proximal Tibia and Related Factors During the First Year of Spinal Cord Injury.

BackgroundSpinal cord injury (SCI) can lead to disuse osteoporosis. The most vulnerable sites for fragility-induced fractures are the distal femur (DF) and proximal tibia (PT). The aim of this study was to evaluate changes in bone mineral density (BMD) at the DF and PT, as well as related factors, during the first year of SCI.Patients and MethodsThirty-six SCI patients within 12 months of their injury were selected, as were 36 healthy controls. The dual-energy X-ray absorptiometry was used to measure BMDs at the DF, PT, and hip of all subjects. According to the duration of SCI when receiving DXA scan, 36 SCI patients were divided into three subgroups. The BMDs of overall patients and subgroups were compared to those of controls. Biochemical markers of bone metabolism were detected in SCI patients.ResultsThe BMDs at the DF, PT, and hips of overall SCI patients were significantly lower than those of controls. The percentage difference of BMD between SCI patients and controls at the DF and PT was higher than at the hip. The BMD at the PT of SCI within 6 weeks post-injury was lower than that of controls. The BMDs at the DF and PT of SCI during 6 weeks-3 months post-injury were lower than those of controls. Whereas there was no difference in the BMD at the hip during the first 3 months of SCI. Age and 25OHD were the influencing factors of DF BMD. Age and gender were found to influence PT BMD.ConclusionThe rapid loss of BMD at the PT and DF during the first year of SCI occurred significantly earlier than that of the hip. It is recommended to monitor the BMD of DF and PT in early-stage SCI patients, combined with detection of biochemical markers of bone metabolism.

Oral bisphosphonate treatment in patients with Duchenne muscular dystrophy on long term glucocorticoid therapy

Osteoporosis is a major problem in patients with Duchenne muscular dystrophy (DMD), due to glucocorticoid therapy and muscle weakness. Evidence on which to base optimal prevention and treatment strategies, including bisphosphonate use, in DMD are limited. Our objective was to describe bone health outcomes of oral alendronate treatment in patients with DMD and glucocorticoid-induced osteoporosis. We retrospectively studied 54 patients treated between 2005 and 2017, and assessed changes in dual-energy x-ray absorptiometry (DXA) whole body and lumbar spine bone mineral density and content, and lateral distal femur bone mineral density. We also examined vertebral fracture development in a subset with serial spine radiographs. Pre-alendronate DXA Z-score trajectories decreased progressively. Over three years post-alendronate initiation, Z-score trajectories improved (p<0.01) at most sites compared with pre-alendronate trajectories. Height-adjusted Z-score trajectories for lumbar spine bone mineral density (p = 0.01) and whole body bone mineral content (p = 0.0004) also improved. The positive trajectories did not seem to be sustained long term in those treated up to 6 years. Radiographic vertebral findings in 43 patients appeared stable. In conclusion, oral bisphosphonate therapy using alendronate was associated with improvement of DXA bone health indices during the first three years of treatment, and may help mitigate progression of osteoporosis in glucocorticoid-treated patients with DMD.

An Exploratory Study of the Texture Research Investigational Platform (TRIP) to Evaluate Bone Texture Score of Distal Femur DXA Scans – A TBS-Based Approach

Poor bone status is associated with increased complications following orthopedic surgery. Therefore, assessing site-specific skeletal status prior to or after orthopedic surgery to optimize outcomes is appealing. The trabecular bone score (TBS) approach, a surrogate for microarchitecture, was adapted to the Texture Research Investigational Platform (TRIP), which allows assessment of many skeletal sites imaged by various modalities. TRIP generates a bone texture score (TBS ORTHO), which could potentially guide surgical decision-making and offer insight into postsurgical fracture risk. As distal femur bone loss occurs following total knee arthroplasty (TKA), we hypothesized that TBS ORTHO after TKA would identify poorer texture in the operated femur compared to the nonoperated. We evaluated 30 subjects (15 M/15 F) with unilateral TKA 2–5 yr previously, mean age 67.9 yr and body mass index 30 kg/m2. Using a Lunar iDXA, lumbar spine and entire femur scans were obtained, the latter using the atypical femur fracture feature. Distal femur bone mineral density (BMD) and TBS ORTHO were obtained using manual regions of interest (ROI) at 15% and 25% of leg length from the intercondylar notch. TBS ORTHO was determined using distal femur DICOM images and TRIP v1.0 (Medimaps, France). Differences in operated vs nonoperated femur were evaluated by paired t test. As previously reported, operated leg BMD was approx 10% lower at 15% and 25% ROIs. Similarly, TBS ORTHO values in the operated leg were approx 5% lower (p < 0.05) at these same ROIs. Distal femur TBS ORTHO and BMD were largely unrelated. TBS ORTHO reproducibility at these ROIs was approx 3.5%. In conclusion, this pilot study documents the feasibility of reproducibly obtaining distal femur TBS ORTHO values. Lower values were observed in the surgical leg, consistent with the bone loss that follows TKA. Further work is indicated to refine TRIP use and evaluate whether such data provides guidance for surgical decision-making and improves periprosthetic fracture prediction.

DXA Measured Distal Femur Bone Mineral Density in Patients After Total Knee Arthroplasty: Method Development and Reproducibility

Introduction: Total knee arthroplasty (TKA) is increasingly being performed. Distal femur periprosthetic fracture is a potentially catastrophic complication following TKA and existing data document substantial distal femur bone mineral density (BMD) loss following TKA. However, distal femur BMD is virtually never measured clinically as no consensus approach exists. This pilot study's purpose was to define regional BMD variation throughout the femur, suggest standard dual-energy X-ray absorptiometry (DXA) regions of interest (ROIs) and evaluate BMD reproducibility at these ROIs. Methods: Thirty volunteers 2–5 yr post TKA had both entire femurs imaged twice using a Lunar iDXA with subject repositioning between scans; the atypical femur fracture feature of enCORE software was utilized. To define femoral BMD distribution, custom 1 cm ROIs were stacked one atop the other starting at the intercondylar notch and continuing to the base of the lesser trochanter. Femur length was measured with the ruler tool to calculate distance at 5% increments. ROIs encompassing each 5% increment were utilized to measure BMD at each location. Descriptive statistics were used to determine mean BMD at each ROI and reproducibility at the 15%, 25%, 45%, 60%, and 80% ROIs. Results: The 5 and 10% ROIs included prosthetic and/or patella, causing high BMD values. Distal femur BMD was lowest at the 15% ROI and was higher (p < 0.05) at each more proximal ROI to 45%, then plateaued from 45% to 75%. BMD reproducibility at these regions was excellent; coefficient of variation (CV) from ∼1% to 3.5%. As periprosthetic fractures generally occur in the distal femur, we propose measuring femur BMD using ROIs placed at 15% and 25%. A 60% region could also be used as a highly cortical site. Conclusion: Existing DXA capabilities allow distal femur BMD measurement with good reproducibility. Further research using standardized ROIs to assess distal femur BMD loss after TKA, and interventions to mitigate this loss, is indicated.

Normative data for lateral distal femur bone mineral density in children from 3 to 18 years of age using Lunar Prodigy absorptiometry

Normative data for lateral distal femur bone mineral density in children from 3 to 18 years of age using Lunar Prodigy absorptiometry

Effects of short-term glucocorticoid administration on bone mineral density, biomechanics and microstructure in rats' femur.

The effects of short-term use of oral glucocorticoid (GC) on the skeleton are not well defined. To address this gap, the influences of 7 days, 21 days of GC administration on femurs of intact rats were investigated. Forty 4-month-old female Sprague-Dawley rats were randomly divided into control group (Cont) and prednisone-treated group (Pre) and administered either distilled water or prednisone acetate at doses of 3.5 mg/kg/day for 0, 7 and 21 days, respectively. All the femurs were harvested for dual-energy X-ray absorptiometry scan, biomechanical testing and micro computed tomography scan. The whole body weight, femur bone mineral density (BMD), all three-point bending test parameters, microstructural parameters increased or improved significantly in Cont at day 21 when compared to day 0. The whole body weight, distal femur BMD, Young's modulus, bending stiffness, density of tissue volume and trabecular thickness (Tb.Th) decreased, while structure model index and trabecular separation (Tb.Sp) increased significantly in Pre at day 21 when compared to age-matched control but had no significant differences between day 7 and day 21. Our data demonstrate that 7-day use of prednisone does not influence on rats' femur, and 21-day use of prednisone slows in rate of whole body weight gain, decreases femur metaphysis BMD and bone stiffness which mainly due to the deteriorated bone microstructure.

Bone mineral density in MPS IV A (Morquio syndrome type A).

Mucopolysaccharidosis IV A (MPS IV A), Morquio A, is caused by deficiency in lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS), which is responsible for the catabolism of the glycosaminoglycans (GAGs) keratan sulfate (KS) and chondroitin 6-sulfate (C6S). Accumulation of GAGs results in disrupted cartilage formation and skeletal dysplasia. In this prospective cross-sectional study, bone mineral density (BMD) of the whole body (WB), lumbar spine (LS), and lateral distal femur (LDF) was acquired by dual-energy X-ray absorptiometry (DXA) on patients with MPS IV A. Functional abilities, medical history, Tanner score, and laboratory results were reviewed. Age and sex-matched norms were used to calculate Z-scores. Participants included 18 patients (13 females; 16 were unrelated) with a mean age of 21.4years (3.3 to 40.8years). While every patient was able to bear weight, 9 were full-time ambulators. Whole-body DXA could be obtained on only 6 patients (5 full-time ambulators) because of respiratory compromise caused by the position, presence of hardware, or positioning difficulties. Mean WB Z-score was -2.0 (range-0.3 to -4.1). Technical issues invalidating LS DXA in 8 patients included kyphosis at the thoracolumbar junction resulting in overlap of vertebrae in the posterior-anterior view. Mean LS BMD Z-score in full-time ambulators was -3.4 (range-1.6 to -5.0) and in the non-/partial ambulator was -4.0 (-3.7 to -4.2). Lateral distal femur BMD was acquired on every patient, and average Z-scores were -2 or less at all sites; full-time ambulators exhibited higher BMD. In conclusion, the LDF proved to be the most feasible site to measure in patients with MPS IV A. The higher LDF values in ambulators suggest this should be a consideration in promoting bone health for this group.

The effect of low magnitude mechanical stimulation (LMMS) on bone density in patients with Rett syndrome: a pilot and feasibility study.

Low magnitude mechanical stimulation (LMMS) has been used successfully to promote bone formation in certain patient populations. This study evaluated the feasibility and effectiveness of LMMS on improving bone mineral density (BMD) in patients with Rett syndrome. A 12-month crossover pilot study design of 6 months of intervention with LMMS and 6 months without was studied in 14 subjects divided in two subgroups. BMD was assessed using Dual Energy X-ray Absorptiometry (DXA). The levels of 25-hydroxy vitamin D (25OHD), Parathyroid Hormone (PTH), Insulin-Like Growth Factor 1 (IGF-1), and circulating markers of bone resorption (NTx) were analyzed in blood samples. Health questionnaires and diet logs were obtained at 0, 6, and 12 months. Of the 11 subjects who completed the protocol, 9 had an adherence of > 65% and showed an increase in spine BMD Z-scores from the intervention (Z: -2.51) compared to non-intervention period (Z: -2.27) of 0.23 SD (p=0.048). Following intervention, favorable trends were also observed for IGF-1 (p=0.06) and right distal femur BMD Z-scores (p=0.07). These preliminary results are promising for a larger, placebo-controlled randomized study of subjects with Rett syndrome.

Cathepsin K inhibitors increase distal femoral bone mineral density in rapidly growing rabbits

BackgroundSelective and reversible inhibitors of human Cathepsin K (CatK), including odanacatib (ODN), have been developed as potential therapeutics for the treatment of osteoporosis. Inhibitors of human CatK show significantly less potency for the rodent enzymes compared with that for the human or rabbit enzymes; thus the Schenk model in growing rabbit was developed as a screening assay for the in vivo activity of CatK inhibitors in blocking bone resorption.MethodsIn this study, the efficacy of the selective inhibitors L-833905, L-006235, L-873724, and L-1037536 (ODN) of human CatK in the rapidly growing rabbit ‘Schenk’ model (age seven weeks) was compared to vehicle, using the bisphosphonate, alendronate (ALN), as a positive control, to assess inhibition of bone resorption. An enzyme inhibition assay (EIA) and an in vitro bone resorption assay using rabbit osteoclasts on bovine cortical bone slices were performed to evaluate the potency of these CatK inhibitors. Bone mineral density of the distal femur (DFBMD) was measured after ten days of treatment using ex vivo DXA densitometry.ResultsResults of the EIA using rabbit CatK and the rabbit bone resorption assay showed that three of the four compounds (L-006235, L-873724, and ODN) had similar potencies in the reduction of collagen degradation. L-833905 appeared to be a weaker inhibitor of CatK. Taking into account the respective in vitro potencies and pharmacokinetic profiles via oral administration, the efficacy of these four CatK inhibitors was demonstrated in a dose-related manner in the growing rabbit. Significant increases in DFBMD in animals dosed with the CatK inhibitors compared to vehicle were seen.ConclusionsEfficacy of the CatK inhibitors in the Schenk rabbit correlated well with that in the in vitro rabbit bone resorption assay and in the ovariectomized rabbit model as previously published. Hence, these studies validated the rabbit Schenk assay as a rapid and reliable in vivo model for prioritizing human CatK inhibitors as potential therapeutic agents.

A reliable method for measuring proximal tibia and distal femur bone mineral density using dual-energy X-ray absorptiometry

PurposeTo assess the intra- and inter-rater reliability of a standardized protocol for measuring proximal tibia and distal femur bone mineral density (BMD) using dual-energy X-ray absorptiometry (DXA). MethodsTen able-bodied individuals (7 males) participated in this study. During one measurement session, the knee of each participant was scanned twice by rater 1 using DXA. Both scans were analyzed twice by rater 1 as well as once by a second rater. Intraclass correlation coefficients (ICCs), standard error of measurements (SEMs) and smallest detectable differences (SDDs) were calculated for the outcome measures proximal tibia and distal femur BMD. A decision study was performed to determine the effect of study protocol adjustments (i.e. increasing the number of scan repetitions, or scan analyses by the same rater) on SEM and SDD values. ResultsHigh intra- and inter-rater ICCs (0.97–0.98) were found for both proximal tibia and distal femur BMD. Low SEMs (0.017–0.028g/cm2) and SDDs (0.047–0.077g/cm2) were found, with a slightly better result for proximal tibia BMD. Increasing the number of scan analyses by the same rater did not markedly reduce SEM and SDD values, while increasing the number of scan repetitions did. ConclusionsProximal tibia and distal femur BMD can be reliably assessed with this method.

Differences in the stress distribution in the distal femur between patellofemoral joint replacement and total knee replacement: a finite element study

BackgroundPatellofemoral joint replacement is a successful treatment option for isolated patellofemoral osteoarthritis. However, results of later conversion to total knee replacement may be compromised by periprosthetic bone loss. Previous clinical studies have demonstrated a decrease in distal femoral bone mineral density after patellofemoral joint replacement. It is unclear whether this is due to periprosthetic stress shielding. The main objective of the current study was to evaluate the stress shielding effect of prosthetic replacement with 2 different patellofemoral prosthetic designs and with a total knee prosthesis.MethodsWe developed a finite element model of an intact patellofemoral joint, and finite element models of patellofemoral joint replacement with a Journey PFJ prosthesis, a Richards II prosthesis, and a Genesis II total knee prosthesis. For each of these 4 finite element models, the average Von Mises stress in 2 clinically relevant regions of interest were evaluated during a simulated squatting movement until 120 degrees of flexion.ResultsDuring deep knee flexion, in the anterior region of interest, the average Von Mises stress with the Journey PFJ design was comparable to the physiological knee, while reduced by almost 25% for both the Richards II design and the Genesis II total knee joint replacement design. The average Von Mises stress in the supracondylar region of interest was similar for both patellofemoral prosthetic designs and the physiological model, with slightly lower stress for the Genesis II design.ConclusionsPatellofemoral joint replacement results in periprosthetic stress-shielding, although to a smaller degree than in total knee replacement. Specific patellofemoral prosthetic design properties may result in differences in femoral stress shielding.

Bone Mineral Density in Spinal Cord Injury: An Evaluation of the Distal Femur

Osteoporosis (OP) in spinal cord injury (SCI) patients is a secondary process in which numerous factors are involved. Diagnosing OP and the threshold for fractures in this population, based on bone mineral density (BMD) measured by double energy X-ray absorptiometry (DXA), is still a challenge. The aim of this study was to evaluate bone mineral loss by DXA, its relationship with body composition and fracture incidence, in complete paraplegics patients, compared with aged-matched controls; we include a nonstandard bone site, the distal femur, and describe the technical and practical aspects of this procedure. Twenty-five SCI patients were included in the study and 17 subjects as control group. No prior or recent fractures were observed in X-ray analysis. The BMD of all femoral sites was significantly lower in patients than in controls (femoral neck, total femur, and distal femur); no difference was observed between BMD of the lumbar spine of patients and controls. We found inverse relationship between time of SCI and bone mineral mass only for distal femur BMD. We conclude that the distal femur is a more sensitive bone site for assessing bone loss by DXA, in SCI patients, than the proximal femoral sites.

Normal epidermal growth factor receptor signaling is dispensable for bone anabolic effects of parathyroid hormone

Although the bone anabolic properties of intermittent parathyroid hormone (PTH) have long been employed in the treatment of osteoporosis, the molecular mechanisms behind this action remain largely unknown. Previous studies showed that PTH increases the expression and the activity of epidermal growth factor receptor (EGFR) in osteoblasts, and activation of ERK1/2 by PTH in osteoblasts was demonstrated to induce the proteolytical release of EGFR ligands and EGFR transactivation. However, conclusive evidence for an important role of the EGFR system in mediating the anabolic actions of intermittent PTH on bone in vivo is lacking. Here, we evaluated the effects of intermittent PTH on bone in Waved-5 (Wa5) mice which carry an antimorphic Egfr allele whose product acts as a dominant negative receptor. Heterozygous Wa5 females and control littermates received a subcutaneous injection of PTH (80 μg/kg) or buffer on 5 days per week for 4 weeks. Wa5 mice had slightly lower total bone mineral density (BMD), but normal cancellous bone volume and turnover in the distal femoral metaphysis. The presence of the antimorphic Egfr allele neither influenced the PTH-induced increase in serum osteocalcin nor the increases in distal femoral BMD, cortical thickness, cancellous bone volume, and cancellous bone formation rate. Similarly, the PTH-induced rise in lumbar vertebral BMD was unchanged in Wa5 relative to wild-type mice. Wa5-derived osteoblasts showed considerably lower basal extracellular signal-regulated kinase 1/2 (ERK1/2) activation as compared to control osteoblasts. Whereas activation of ERK1/2 by the EGFR ligand amphiregulin was largely blocked in Wa5 osteoblasts, treatment with PTH induced ERK1/2 activation comparable to that observed in control osteoblasts, relative to baseline levels. Our data indicate that impairment of EGFR signaling does not affect the anabolic action of intermittent PTH on cancellous and cortical bone.

Poster 40 Effects of Cycling on Bone and Muscle in Pediatric Spinal Cord Injury

Determine the effect of cycling with and without functional electrical stimulation (FES) on bone mineral density (BMD), muscle volume, and stimulated strength in pediatric spinal cord injury (SCI). Randomized controlled trial. Pediatric referral hospital. Thirty children, ages 5 to 13 years, with motor complete SCI. Children were randomized to FES cycling (FESC), passive cycling (PC), or electrically-stimulated exercise (ES) and exercised one hour, three times/week for 6 months. BMD via dual-energy x-ray absorptiometry (DXA), muscle volume via magnetic resonance imaging (MRI), and isometric stimulated strength on a computerized dynamometer. The FESC group increased hip, distal femur, and proximal tibia BMD by 32.4%, 6.62% and 10.3%, respectively. The PC group increased at the hip (29.2%), but not at the distal femur (1.5%) or proximal tibia (−1.0%). The ES group had no change at the hip (−0.24%) or distal femur (3.3%) and declined at the proximal tibia (−7.06%). For quadriceps volume and stimulated strength, ES led to greater changes in volume and FESC to greater changes in strength. Within groups, quadriceps volume and strength increased following FESC, and quadriceps volume increased following ES. Average percent changes were: quadriceps volume (FESC 24.4%, PC 7%, 27%), hamstrings volume (FESC 19.8%, PC 3.1%, ES 12.5%), quadriceps stimulated strength (FESC 137.1%, PC 33.0%, ES 96.2%), and hamstrings stimulated strength (FESC 1.2%, PC −20.5%, ES −27.3%). Positive effects were seen on muscle for groups using electrical stimulation and possibly bone for children who cycled, which may reduce the risk of cardiovascular disease and fractures. Some BMD gains made were greater than anticipated due to growth, and muscle volume changes are not anticipated following strengthening in children without disability, suggesting that changes were clinically meaningful.

Effects of cycling and/or electrical stimulation on bone mineral density in children with spinal cord injury

Randomized clinical trial. To determine the effect of cycling and/or electrical stimulation on hip and knee bone mineral density (BMD) in children with spinal cord injury (SCI). Children's hospital specializing in pediatric SCI. A total of 30 children, aged 5-13 years, with chronic SCI were randomized to one of three interventions: functional electrical stimulation cycling (FESC), passive cycling (PC), and non-cycling, electrically stimulated exercise (ES). Each group exercised for 1 h, three times per week for 6 months at home. The hip, distal femur and proximal tibia BMD were examined via dual-energy X-ray absorptiometry (DXA) pre- and post-intervention. In all, 28 children completed data collection. The FESC group exhibited increases in hip, distal femur and proximal tibia BMD of 32.4, 6.62 and 10.3%, respectively. The PC group exhibited increases at the hip (29.2%), but no change at the distal femur (1.5%) or proximal tibia (-1.0%). The ES group had no change at the hip (-0.24%) and distal femur (3.3%), but a loss at the proximal tibia (-7.06%). There were no differences between groups or within groups over time. Significant negative correlations were found between baseline BMD and the amount of BMD change. Although not achieving statistical significance, hip BMD changes observed were greater than the reported 0.9-10% gains after exercise for children with and without disability. Thus, cycling with and without electrical stimulation may be beneficial for skeletal health in pediatric SCI, but further research is needed with a larger sample size.