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Biomedical subjects

J D Wark

Publications and source records attributed to J D Wark.

At least 19 recordsLinked to original sources
PubMed2001

Low-intensity pulsed ultrasound stimulates a bone-forming response in UMR-106 cells.

Low-intensity (<100 mW/cm(2)) pulsed ultrasound (US) is an established therapy for fracture repair. In both animal and human trials, such US has been shown to facilitate fresh fracture repair and initiate healing in fractures with repair defects. However, the mechanism by which US achieves these outcomes is not clear. One possible mechanism is the direct stimulation of bone formation. To investigate this hypothesis, the current study investigated the mRNA response of isolated bone-forming cells (UMR-106 cells) to a single 20-min dose of low-intensity pulsed US. Using a novel US-cell coupling method, US was found to stimulate expression of the immediate-early response genes c-fos and COX-2 and elevate mRNA levels for the bone matrix proteins ALP and OC. These findings suggest that low-intensity pulsed US has a direct effect on bone formation. This may contribute to the beneficial effect of low-intensity pulsed US on fracture repair.

Alkaline Phosphatase↗
PubMed2001

Changes in body composition as determinants of longitudinal changes in bone mineral measures in 8 to 26-year-old female twins.

Between 1990 and 1998, we conducted a longitudinal study of 286 female twins aged 8 to 25 years at baseline (60 monozygotic (MZ) pairs, 44 dizygotic (DZ) pairs and 78 unpaired twins), measured on average 2.4 times (range 2-6) with an average of 1.8 years between measurements (range 0.7-6.7 years). Areal bone mineral density (ABMD) at the lumbar spine, total hip and femoral neck, total body bone mineral content (BMC), total body soft tissue composition (lean mass and fat mass) were measured by dual-energy X-ray absorptiometry, and height and menarchial status were also recorded. Median annual changes in height were negligible at 4 years post-menarche. During the 'linear growth' period up to 4 years post-menarche, ABMD at the lumbar spine, total hip and femoral neck increased with annual change in lean mass by 1.7 (S.E.0.1), 1.4 (0.1) and 1.0 (0.1) percent per kilogram per year, respectively (all p<0.001), independently of changes in fat mass or height. During the 'post-linear growth' period, ABMD at the total hip and femoral neck increased with annual change in fat mass by 0.3 (0.1) and 0.5 (0.1) percent per kilogram per year (all p < 0.01), independent of change in lean mass. Annual changes in total body BMC were associated with annual changes in lean mass (1.9 (0.2) percent per kilogram), in fat mass (1.3 (0.2) percent per kilogram) and in height (0.7) (0.2) percent per centimeter) during linear growth, and in fat mass (1.0 (0.1)) and lean mass (0.6 (0.1)) percent per kilogram post-linear growth (all p < 0.001). We conclude that changes in bone mineral measures are strongly associated with changes in lean mass during linear growth, while post-linear growth, changes in fat mass are the predominant, although weaker, predictor. These findings suggest that the strong cross-sectional association between bone mineral measures and lean mass is established during growth and development, and that fat mass emerges as a more powerful determinant of bone change in healthy adult females.

Absorptiometry, Photon↗
PubMed2001

Skeletal effects of low-intensity pulsed ultrasound on the ovariectomized rodent.

Growing evidence supports low-intensity pulsed ultrasound (US) as an osteogenic mechanical stimulus. Its effects on isolated bone cells and on fractured bone are established. However, its effects on osteoporosis are not clear. This study examined US effects on ovariectomy (OVX) induced bone changes within the rodent hindlimb (distal femur and proximal tibia), and on normal bone in animals following sham-OVX. Animals were exposed to daily unilateral active-US and contralateral inactive-US for 12 weeks. Bone status was assessed using dual energy X-ray absorptiometry and histomorphometry. Ovariectomy resulted in significant bone changes. Low-intensity pulsed US did not influence these changes. These results suggest that the US dose introduced may not be a beneficial treatment for osteoporosis, and that intact bone may be less sensitive to US than fractured bone and isolated bone cells. This may relate to the biophysical mechanisms of action of US, US-bone interactions and tissue level processes taking place.

Absorptiometry, Photon↗
PubMed2001

Efficacy of low-intensity pulsed ultrasound in the prevention of osteoporosis following spinal cord injury.

Ultrasound (US), a high-frequency acoustic energy traveling in the form of a mechanical wave, represents a potential site-specific intervention for osteoporosis. Bone is a dynamic tissue that remodels in response to applied mechanical stimuli. As a form of mechanical stimulation, US is anticipated to produce a similar remodeling response. This theory is supported by growing in vitro and in vivo evidence demonstrating an osteogenic effect of pulsed-wave US at low spatial-averaged temporal-averaged intensities. The aim of this study was to investigate whether low-intensity pulsed US could prevent calcaneal osteoporosis in individuals following spinal cord injury (SCI). Fifteen patients with a 1-6 month history of SCI were recruited. Active US was introduced to one heel for 20 min/day, 5 days/week, over 6 weeks. The contralateral heel was simultaneously treated with inactive US. Patients were blind to which heel was being actively treated. Active US pulsed with a 10 microsec burst of 1.0 MHz sine waves repeating at 3.3 kHz. The spatial-averaged temporal-averaged intensity was set at 30 mW/cm(2). Bone status was assessed at baseline and following the intervention period by dual-energy X-ray absorptiometry and quantitative US. SCI resulted in significant bone loss. Bone mineral content decreased by 7.5 +/- 3.0% in inactive US-treated calcanei (p < 0.001). Broadband US attenuation and speed of sound decreased by 8.5 +/- 6.9% (p < 0.001) and 1.5 +/- 1.3% (p < 0.001), respectively. There were no differences between active and inactive US-treated calcanei for any skeletal measure (p > 0.05). These findings confirm the negative skeletal impact of SCI, and demonstrate that US at the dose and mode administered was not a beneficial intervention for SCI-induced osteoporosis. This latter finding may primarily relate to the inability of US to effectively penetrate the outer cortex of bone due to its acoustic properties.

Absorptiometry, Photon↗
PubMed2001

Relationships with serum parathyroid hormone in old institutionalized subjects.

OBJECTIVE AND BACKGROUND: Old people in residential care are at the highest risk of any group for hip fracture. This may relate to their high prevalence of hyperparathyroidism. There are few data, however, on relationships with serum parathyroid hormone (PTH) in these individuals. This study therefore examined complex associations with serum PTH in nursing home and hostel residents. DESIGN: Cross-sectional analysis. PATIENTS: One hundred and forty-three nursing home and hostel residents of median age 84 years. MEASUREMENTS: Serum PTH, 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D (1,25-(OH)2D), plasma creatinine, phosphate, calcium, albumin, Bsm-1 vitamin D receptor genotype, age, weight and use of frusemide or thiazide. RESULTS: The statistical models determined accounted for half the interindividual variation in serum PTH. Heavier weight was associated with both the prevalence of secondary hyperparathyroidism and the serum concentration of PTH. Novel interactions with serum PTH were identified between: weight and 25OHD; 25OHD and phosphate; and phosphate and thiazide diuretic use. Plasma phosphate was associated with PTH independently of calcium and 1,25-(OH)2D. There was no independent association between PTH and nuclear vitamin D receptor genotype. CONCLUSIONS: Heavier weight is associated with both the prevalence and severity of secondary hyperparathyroidism and consistent with animal models of secondary hyperparathyroidism, phosphate may relate to serum PTH independently of 1,25-(OH)2D or calcium.

Aged↗
PubMed2001

An effective, economic way of monitoring menstrual cycle hormones in at risk female athletes.

PURPOSE: Female athletes, in response to intensive training, competition stress and a lean, athletic physique, are at increased risk of altered hypothalamic-pituitary ovarian (HPO) axis function associated with menstrual cycle disturbance and reduced secretion of the ovarian hormones estrogen and progesterone. Because there is evidence suggesting possible detrimental effects on skeletal health associated with deficiencies in these hormones, a suitable means to asses ovarian hormone concentrations in at risk athletes is needed. The aim of this study was to evaluate a simple, economical means to monitor the ovarian hormone production in athletes, in the setting of intensive training. METHODS: Subjects comprised 14 adolescent rowers, 12 lightweight rowers, and two groups of 10 matched control subjects. Ovarian function was monitored during the competition season by estimation of urinary excretion of estrone glucuronide (E1G) and pregnanediol glucuronide (PdG), enabling the menstrual cycles to be classified as ovulatory or anovulatory. RESULTS: Results indicated 35% and 75% of schoolgirl and lightweight rowers had anovulatory menstrual cycles, respectively. These findings were highlighted by significantly lower excretion of E1G and PdG during phases of intensive training in both the lightweight and schoolgirl rowers, compared with the control subjects. CONCLUSION: It was concluded that the urinary E1G and PdG assays were an effective means to assess the influence of intense training on ovarian hormone concentrations in at risk athletes. It is recommended that this technique be applied more widely as a means of early detection of athletes with low estrogen and progesterone levels, in an attempt to avoid detrimental influences on skeletal health.

Adolescent↗
PubMed2001

Effects of calcitriol or calcium on bone mineral density, bone turnover, and fractures in men with primary osteoporosis: a two-year randomized, double blind, double placebo study.

Osteoporosis in men is an emerging public health problem. As calcitriol reduces the rate of vertebral fractures in osteoporotic postmenopausal women, we conducted a prospective study of this treatment in men with primary osteoporosis. Our study was a 2-yr, randomized, double masked, double placebo-controlled trial of calcitriol (0.25 microg twice daily) or calcium (500 mg twice daily) in 41 men with primary osteoporosis and at least 1 baseline fragility fracture. Thirty-three men (85%) completed the study. There were no differences in baseline characteristics. Spinal and femoral neck bone mineral densities at 2 yr were unchanged in both groups. Serum osteocalcin decreased in both groups by 30% (P < 0.05), whereas urine N-telopeptide cross-links decreased only in the calcium group by 30% (P < 0.05). After 2 yr, fractional calcium absorption increased by 34% (P < 0.01) in the calcitriol group. Nineteen incident fragility fractures occurred (14 vertebral and 5 nonvertebral) in 7 men. Over 2 yr, the number of men with vertebral fractures (6 vs. 1; P = 0.097) was similar in both groups. In conclusion, the efficacy of calcitriol remains unproven as a single agent for the treatment of osteoporosis in men.

Adult↗
PubMed2001

The effects of +Gz force on the bone mineral density of fighter pilots.

HYPOTHESIS: Bone is a metabolically active tissue which responds to high strain loading. The purpose of this study was to examine the bone response to high +Gz force loading generated during high performance flying. METHODS: The bone response to +Gz force loading was monitored in 10 high performance RAAF pilots and 10 gender-, age-, height-, weight-matched control subjects. The pilots were stationed at the RAAF base at Pearce, Western Australia, all completing the 1-yr flight training course. The pilots flew the Pilatus PC-9 aircraft, routinely sustaining between 2.0 and 6.0 +Gz. Bone mineral density (BMD) and bone mineral content (BMC) were measured at baseline and 12 mo, using the Hologic QDR 2000+ bone densitometer. RESULTS: After controlling for change in total body weight and fat mass, the pilots experienced a significant increase in BMD and BMC for thoracic spine, pelvis, and total body, in the magnitude of 11.0%, 4.9%, and 3.7%, respectively. However, no significant changes in bone mineral were observed in the pilots lumbar spine, arms or legs. The control group experienced a significant decrease in pelvic BMC, with no other bone mineral changes observed at any site. CONCLUSIONS: These findings suggest that site specific BMD is increased in response to high +Gz forces generated during high performance flying in a PC-9.

Adaptation, Physiological↗
PubMed2000

Acceleration of fresh fracture repair using the sonic accelerated fracture healing system (SAFHS): a review.

The Sonic Accelerated Fracture Healing System (SAFHS) is a relatively new fracture management tool which incorporates the application of a specifically modified diagnostic ultrasound unit to healing fractures with the intention of accelerating repair. In an animal fracture model, this device has been shown to accelerate the rate of biomechanical healing by a factor of 1.4-1.6. In two randomized, controlled trials in humans, the same unit has been shown to reduce the time frame of clinical and radiographic healing by 38%. In the two fracture regions investigated, tibial diaphysis and distal radius, this represented a 58 day and 37 day reduction in healing time, respectively. Despite its effect on the entire process of fresh fracture repair, the effect of the SAFHS on the individual stages and processes involved has not been established. This paper reviews these stages and processes, and discusses the clinical and practical implications of the effect of the SAFHS on fracture repair and the need for further research into this modality.

Animals↗
PubMed2000

Does childhood and adolescence provide a unique opportunity for exercise to strengthen the skeleton?

Osteoporosis is a major, and increasing, public health problem. In this review we examine the evidence that childhood physical activity is an important determinant of bone mineral in adult years, and as such, may help to prevent osteoporosis. Animal studies provide incontrovertible evidence that growing bone has a greater capacity to add new bone to the skeleton than does adult bone. Observational studies in children undertaking routine physical activity and cross-sectional athlete studies in young sportspeople both reveal that activity is positively associated with bone mineral density (BMD). Longitudinal studies in pre- and peripubertal gymnasts reveal BMD gains far in excess of those that can be achieved in adulthood. However, such studies permit only limited conclusions as they contain the potential for selection bias and can be confounded by other determinants of bone mineral (e.g. dietary and lifestyle factors). Thus, research comparing inter-individual playing-to-nonplaying arm differences in bone mineral (e.g., in racquet sports) have proven to be extremely useful. These studies suggest that the BMD differences are clearly greater when bone is subjected to mechanical loading prior to the end of puberty and longitudinal growth of the body (in women, before menarche) rather than after it. Tanner stage II and III appears to be the maturational stage when the association between exercise and BMD becomes manifest in most adolescents. Do conclusions drawn from athlete studies apply to the general population? Randomised intervention studies of physical activity and bone mineral accrual in normal children confirm that childhood activity is strongly associated with bone mineral accrual. Furthermore, some retired athlete studies and a detraining study suggest that adolescent bone gain may, at least partly, persist despite reduced adult physical activity. Mechanisms that may underlie the association between childhood physical activity and bone mineral accrual are outlined. Thus, it appears that physical activity during the most active period of maturity (with respect to longitudinal growth of the body) plays a vital role in optimising peak bone mass and that benefits may extend into adulthood.

Adult↗
PubMed2000

Studies of surgical outcome after patellar tendinopathy: clinical significance of methodological deficiencies and guidelines for future studies. Victorian Institute of Sport Tendon Study Group.

Patellar tendinopathy is often treated surgically after failure of conservative treatment but clinical experience suggests that results are not uniformly excellent. The aim of this review was to (i) identify the different surgical techniques that have been reported and compare their success rates, and (ii) critically assess the methodology of studies that have reported surgical outcomes. Twenty-three papers and two abstracts were included in the review. Surgical procedures were categorized and outcomes summarized. Using ten criteria, an overall methodology score was derived for each paper. Criteria for which scores were generally low (indicating methodological deficiency) concerned the type of study, subject selection process and outcome measures. We found a negative correlation between papers' reported success rates and overall methodology scores (r= -0.57, P<0.01). There was a positive correlation between year of publication and overall methodology score (r=0.68, P<0.001). We conclude that study methodology may influence reported surgical outcome. We suggest practical guidelines for improving study design in this area of clinical research, as improved study design would provide clinicians with a more rigorous evidence-base for treating patients who have recalcitrant patellar tendinopathy.

Bias↗
PubMed2000

Urine calcium and urine sodium concentrations are not related, after adjustment for urine magnesium.

BACKGROUND AND OBJECTIVES: Urine calcium correlates with urine sodium. The aims of this study were to investigate whether the urine sodium-calcium relationship persists into old age and whether it holds after adjustment for urine magnesium. DESIGN: Cross-sectional descriptive analysis. PATIENTS: Residents of two aged care institutions (median age 84 years) who were not taking diuretics, calcium or vitamin D supplements. MEASUREMENTS: Early morning urine calcium, sodium and magnesium, plasma creatinine and serum 25-hydroxyvitamin D and parathyroid hormone. RESULTS: Urine calcium correlated with urine sodium (r = 0.29, P < 0.01) and with urine magnesium (r = 0.56, P < 0.001). After adjustment for urine magnesium, the relationship between urine sodium and urine calcium was no longer significant. Forty-five percent of the interindividual variation in urine calcium was explained by a linear model on the basis of urine magnesium and plasma creatinine. CONCLUSION: The data indicate that a correlation between urine sodium and calcium persists in very old age. However, this correlation no longer holds after adjustment for urine magnesium. Further studies examining urine calcium excretion should also consider urine magnesium.

25-Hydroxyvitamin D 2↗
PubMed2000

Determination of age at death using combined morphology and histology of the femur.

Bone is characterised by age-related morphological and histological changes. We have previously established an automated method of recording bone morphometry and histology from entire transverse sections of cortical bone. Our aim was to determine whether data acquired using this automated system were useful in the prediction of age. Ninety-six specimens of human femoral middiaphysis were studied from subjects aged 21-92 y. Equations predicting specimen age were constructed using macroscopic data (total subperiosteal area (TSPA), periosteal perimeter (PP), endosteal perimeter (EP), cortical bone area (CA) and moments of area) and microscopic data (the number, size and diversity of pores and intracortical porosity) together with sex, height and weight. Both TSPA and PP were independent predictors of age but the number of pores was not a significant predictor of age in any equation. The age predicted by these equations was inaccurate by more than 8 y in over half the subjects. We conclude that we could not predict age at a clinically acceptable level using data from our automated system. This most likely reflects an insensitivity to regional age-related changes in bone histology because we recorded data from each entire cortex. Automated bone measurement according to cortical region might be more useful in the prediction of age. The inclusion of TSPA together with PP as independent predictors of age raises the possibility that a future measure of periosteal shape at the femoral diaphysis could also be helpful in the prediction of age. The accuracy reached with the relatively simple methods described here is sufficient to encourage the development of image-analysis systems for the automatic detection of more complex features.

Adult↗
PubMed2000

Compressive and shear force generated in the lumbar spine of female rowers.

Rowers have and accrue greater lumbar spine bone mineral density (BMD) associated with mechanical loading produced during rowing. The aim of this study was to estimate the mechanical loading generated at the lumbar spine (LS) that is apparently providing an osteogenic benefit. The cohort comprised 14 female rowers (average age: 19.7yrs; height: 170.9 cm, weight: 59.5 kg) and 14 female matched controls (average age: 20.9 m yrs; height: 167.5 cm; weight: 58.1 kg). BMD was assessed using the Hologic QDR 2000+ bone densitometer, indicating higher lumbar spine BMD in the rowers compared to the control subjects (1,069 +/- 0.1 vs. 1,027 +/- 0.1 g/cm2). No significant difference existed for BMD at any other site. All rowers performed a six-minute simulated race on a Concept II rowing ergometer. Mechanical loading generated at the lumbar spine during this task was assessed using a two-dimensional model of the spine, enabling the calculation of the compressive and shear forces at L4/L5. The shear force was the joint reaction force perpendicular to the spine at the L4/L5 joint. Peak compressive and shear force at the lumbar spine of the rowers were 2,694 +/- 609 (N) and 660 +/- 117 (N), respectively. Peak compressive force at the LS relative to body weight was 4.6 times body weight. The literature would suggest that forces of this magnitude, generated at the LS during maximal rowing, may be contributing to the site specific higher LS BMD found in the rowers.

Adolescent↗
PubMed2000

A technique for restraining rodents during hindlimb interventions.

Recently interest has grown in the skeletal effects of external electrophysical modalities. To introduce these modalities into the rodent hindlimb, restraining the animals is often necessary. This report describes a novel restraint device that was highly successful when used on 10 Sprague-Dawley rats for 20 min daily for 6 days each week over a period of 12 weeks. The restrained animals gained less weight than did 10 cage control animals, suggesting that animals experienced stress. However, this weight loss was significant (p < 0.05) only during the first six weeks, suggesting a degree of acclimatization. Restraint had no observable effect on measures of bone mineral content of the hindlimb. The restraint device we developed restrained animals without the need for anesthetics, enabling our device to be used in future studies investigating the skeletal effect of external electrophysical modalities on the rodent hindlimb.

Animal Husbandry↗
PubMed1999

The impact of intense training on endogenous estrogen and progesterone concentrations and bone mineral acquisition in adolescent rowers.

The effect of 18 months of training on the ovarian hormone concentrations and bone mineral density (BMD) accrual was assessed longitudinally in 14 adolescent rowers and 10 matched controls, aged 14-15 years. Ovarian hormone levels were assessed by urinary estrone glucuronide (E(1)G) and pregnanediol glucuronide (PdG) excretion rates, classifying the menstrual cycles as ovulatory or anovulatory. Total body (TB), total proximal femur (PF), femoral neck (FN) and lumbar spine (LS) (L2-4) bone mass were measured at baseline and 18 months using dual-energy X-ray densitometry. Results were expressed as bone mineral content (BMC), BMD and bone mineral apparent density (BMAD). Five rowers had anovulatory menstrual cycles compared with zero prevalence for the control subjects. Baseline TB BMD was significantly higher in the ovulatory rowers, with PF BMD, FN BMD and LS BMD similar for all groups. At completion, the LS bone accrual of the ovulatory rowers was significantly greater (BMC 8.1%, BMD 6.2%, BMAD 6.2%) than that of the anovulatory rowers (BMC 1.1%, BMD 3.9%, BMAD 1.6%) and ovulatory controls (BMC 0.5%, BMD 1.1%, BMAD 1.1%). No difference in TB, PF or FN bone accrual was observed among groups. This study demonstrated an osteogenic response to mechanical loading, with the rowers accruing greater bone mass than the controls at the lumbar spine. However, the exercise-induced osteogenic benefits were less when rowing training was associated with low estrogen and progesterone metabolite excretion.

Adolescent↗
PubMed1999

Correlation of ultrasound and magnetic resonance imaging with clinical outcome after patellar tenotomy: prospective and retrospective studies. Victorian Institute of Sport Tendon Study Group.

OBJECTIVE: To report the appearances of ultrasound (US) and magnetic resonance imaging (MRI) before and after surgery for chronic patellar tendinopathy and to correlate postoperative appearances with clinical outcome. DESIGN: A 12-month prospective longitudinal study and a retrospective study, each part using different patients. Prospective study included clinical assessment, ultrasound, and MRI all performed before and 12 months after surgery. Retrospective study included ultrasound and clinical assessment only (i.e., no MRI) 24 to 67 months after surgery. SETTING: Institutional athlete study group in Australia (Victorian Institute of Sport Tendon Study Group). PATIENTS: In the prospective study, 13 patients (all male; 15 tendons) who underwent patellar tenotomy; in the retrospective study, 17 different patients (18 tendons) who had undergone identical surgery. MAIN OUTCOME MEASURES: Ultrasound and MRI appearances and clinical assessment at baseline and 12 months after surgery (prospective study). Ultrasound appearance and clinical assessment 24 to 67 months after surgery (retrospective study). Dimensions of abnormal regions on imaging were measured. Clinical assessment included categorical rating and numerical Victorian Institute of Sport Assessment (VISA) score. RESULTS: In the prospective study, preoperative ultrasound and MRI appearances confirmed the clinical diagnosis of patellar tendinopathy. Postoperative ultrasound and MRI also revealed abnormalities consistent with patellar tendinopathy. Despite this, 11 of 15 (73%) tendons were rated clinically as either good or excellent. Imaging modalities were unable to distinguish tendons rated as good or excellent from those rated poor at 12 months. In the retrospective study, ultrasound images revealed abnormalities despite full clinical recovery. There was no correlation between dimension of ultrasound abnormality and either VISA score or time since surgery. CONCLUSION: After open patellar tenotomy, MRI and ultrasound findings remain abnormal despite clinical recovery. Thus, clinicians ought to base postoperative management of patients undergoing patellar tenotomy on clinical grounds rather than imaging findings. At present, there appears to be no role for routine postoperative imaging of patients recovering slowly after patellar tenotomy. However, this is not to suggest that imaging cannot play a role in special circumstances.

Adolescent↗