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C C Johnston

Publications and source records attributed to C C Johnston.

At least 19 recordsLinked to original sources
PubMed2005

Bone remodeling at the iliac crest can predict the changes in remodeling dynamics, microdamage accumulation, and mechanical properties in the lumbar vertebrae of dogs.

We previously demonstrated that suppression of bone remodeling allows microdamage to accumulate, thereby leading to reduced bone toughness in dog bone. In this study we evaluated the relationships between bone remodeling at the iliac crest and skeletal activation frequency, microdamage accumulation, or biomechanical properties of lumbar vertebrae using the same dogs to determine whether bone remodeling at the iliac crest can predict damage accumulation and mechanical parameters of the lumbar spine following treatment with antiresorptive agents. Thirty-six female beagles, 1 to 2 years old, were divided into three groups. The control group was treated daily for 12 months with saline vehicle. The remaining two groups were treated daily with oral risedronate at a dose of 0.5 mg/kg/day, or alendronate at 1.0 mg/kg/day orally. The doses of these bisphosphonates were 5 to 6 times the clinical doses approved for treatment of osteoporosis in humans. After sacrifice, the right ilium and L2 vertebra were assigned to histomorphometry. The left ilium and L3 vertebra were used for microdamage analysis. The L4 vertebra was mechanically tested to failure in compression, and bone toughness calculated from the stress-strain curve. There was a strong positive relationship for activation frequency (Ac.f) between ilium and lumbar vertebrae (r2 = 0.82; P < 0.0001). Iliac crest Ac.f underestimates Ac.f in L2, but L2 Ac.f reaches a minimum threshold and does not decline further when iliac crest Ac.f is below 0.10/yr. Microdamage (Cr.S.Dn) accumulation at the ilium was significantly associated with increased microdamage accumulation in the L3 lumbar vertebra (r2 = 0.43, P < 0.0001). The data also show that bisphosphonate treatment increased Cr.S.Dn at a faster rate in L3 than in the iliac crest. Although bisphosphonate treatment decreased bone toughness in L4, this decrease demonstrated no relationship to decreased Ac.f in the ilium. These results clearly indicate that bone remodeling data obtained from iliac crest biopsy could be used to estimate the activation frequency and microdamage burden in the vertebral column.

Administration, Oral↗
PubMed2004

Bisphosphonate treatment affects trabecular bone apparent modulus through micro-architecture rather than matrix properties.

Bisphosphonates are emerging as an important treatment for osteoporosis. But whether the reduced fracture risk associated with bisphosphonate treatment is due to increased bone mass, improved trabecular architecture and/or increased secondary mineralization of the calcified matrix remains unclear. We examined the effects of bisphosphonates on both the trabecular architecture and matrix properties of canine trabecular bone. Thirty-six beagles were divided into a control group and two treatment groups, one receiving risedronate and the other alendronate at 5-6 times the clinical dose for osteoporosis treatment. After one year, the dogs were killed, and samples from the first lumbar vertebrae were examined using a combination of micro-computed tomography, finite element modeling, and mechanical testing. By combining these methods, we examined the treatment effects on the calcified matrix and trabecular architecture independently. Conventional histomorphometry and microdamage data were obtained from the second and third lumbar vertebrae of the same dogs [Bone 28 (2001) 524]. Bisphosphonate treatment resulted in an increased apparent Young's modulus, decreased bone turnover, increased calcified matrix density, and increased microdamage. We could not detect any change in the effective Young's modulus of the calcified matrix in the bisphosphonate treated groups. The observed increase in apparent Young's modulus was due to increased bone mass and altered trabecular architecture rather than changes in the calcified matrix modulus. We hypothesize that the expected increase in the Young's modulus of the calcified matrix due to the increased calcified matrix density was counteracted by the accumulation of microdamage.

Alendronate↗
PubMed2003

Peak spine and femoral neck bone mass in young women.

Achievement of higher peak bone mass early in life may play a critical role against postmenopausal bone loss. Bone mineral density (BMD) of the spine, femoral neck, greater trochanter, Ward's triangle, and spine bone mineral content (BMC) and bone surface area (BSA) were assessed by dual energy x-ray absorptiometry in 300 healthy females (age 6-32 years). Bone measurements were described by using nonlinear models with age, weight, height, or dietary calcium intake as the explanatory variables. At the spine, femoral neck, greater trochanter, and Ward's triangle, the highest BMD level was observed at 23.0 +/- 1.4, 18.5 +/- 1.6, 14.2 +/- 2.0, and 15.8 +/- 2.1 years, respectively. The age of attaining peak spine BMC and BSA cannot be estimated, as significant increases in these two measures were observed through this age group. Age, weight, and height were all significant predictors of all these bone measurements. Weight was a stronger predictor than age for all sites. Dietary calcium intake was not a significant predictor for any of these bone measurements. We conclude that age of attaining peak bone mass at the hip is younger than at the spine, and BMC and BSA at the spine continue to increase through the early thirties in females.

Adolescent↗
PubMed2003

Linkage of structure at the proximal femur to chromosomes 3, 7, 8, and 19.

Risk for osteoporotic fracture is determined in part by femoral structure, which is under genetic control. We conducted a genome scan in 638 sister-pairs for structure phenotypes. Significant evidence of linkage was detected with several chromosomal regions, including confirmation of our prior linkage findings. Bone strength and resistance to fracture at the proximal femur is determined in part by structural variables. We previously reported that several structural variables, including pelvic axis length, femur axis length, femur head width, and femur midshaft width, had significant or suggestive linkage to regions of chromosomes 3, 4, 5, 7, 9, 17, and 19 in a sample of 309 white premenopausal sister pairs. We now report the results of a genome-wide linkage analysis of femoral structure variables in 437 white and 201 black healthy premenopausal sister pairs, of which 191 white pairs overlapped with our previously published sample. Multipoint quantitative linkage analysis was performed using microsatellite markers genotyped throughout the genome. In the current sample, linkage of femoral structure to chromosomes 3, 7, and 19 was confirmed in the white sister pairs, and a new linkage to chromosome 8 was identified. There was linkage at chromosome 3 to femoral head width (logarithm of the odds [LOD] = 5.0) and femur shaft width (LOD = 3.6). On chromosome 19, there was linkage to femoral neck axis length (LOD = 3.2); on chromosome 7, to femoral head width (LOD = 5.0); and on chromosome 8, to femoral head width (LOD = 6.0). The current findings emphasize the importance of increasing sample size to replicate linkage findings and identify new regions of linkage.

Adult↗
PubMed2001

Effects of suppressed bone turnover by bisphosphonates on microdamage accumulation and biomechanical properties in clinically relevant skeletal sites in beagles.

We recently demonstrated that suppression of bone remodeling allows microdamage to accumulate, leading to reduced bone toughness in the rib cortex of dogs. This study evaluates the effects of reduced bone turnover produced by bisphosphonates on microdamage accumulation and biomechanical properties at clinically relevant skeletal sites in the same dogs. Thirty-six female beagles, 1-2 years old, were divided into three groups. The control group was treated daily for 12 months with saline vehicle (CNT). The remaining two groups were treated daily with risedronate at a dose of 0.5 mg/kg per day (RIS), or alendronate at 1.0 mg/kg per day (ALN) orally. The doses of these bisphosphonates were six times the clinical doses approved for treatment of osteoporosis in humans. After killing, the L-1 vertebra was scanned by dual-energy X-ray absorptiometry (DXA), and the L-2 vertebra and right ilium were assigned to histomorphometry. The L-3 vertebra, left ilium, Th-2 spinous process, and right femoral neck were used for microdamage analysis. The L-4 vertebra and Th-1 spinous process were mechanically tested to failure in compression and shear, respectively. One year treatment with risedronate or alendronate significantly suppressed trabecular remodeling in vertebrae (RIS 90%, ALN 95%) and ilium (RIS 76%, ALN 90%) without impairment of mineralization, and significantly increased microdamage accumulation in all skeletal sites measured. Trabecular bone volume and vertebral strength increased significantly following 12 month treatment. However, normalized toughness of the L-4 vertebra was reduced by 21% in both RIS (p = 0.06) and ALN (p = 0.05) groups. When the two bisphosphonate groups were pooled in a post hoc fashion for analysis, this reduction in toughness reached statistical significance (p = 0.02). This study demonstrates that suppression of trabecular bone turnover by high doses of bisphosphonates is associated with increased vertebral strength, even though there is significant microdamage accumulation and a reduction in the intrinsic energy absorption capacity of trabecular bone.

Animals↗
PubMed2001

Effects of high-dose etidronate treatment on microdamage accumulation and biomechanical properties in beagle bone before occurrence of spontaneous fractures.

We recently demonstrated that suppressed bone remodeling allows microdamage to accumulate and causes reductions in some mechanical properties. However, in our previous study, 1 year treatment with high-dose etidronate (EHDP) did not increase microdamage accumulation in most skeletal sites of dogs in spite of complete remodeling suppression and the occurrence of spontaneous fractures of ribs and/or thoracic spinous processes. This study evaluates the effects of EHDP on microdamage accumulation and biomechanical properties before fractures occur. Thirty-six female beagles, 1-2 years old, were treated daily for 7 months with subcutaneous injections of saline vehicle (CNT) or EHDP at 0.5 (E-low) or 5 mg/kg per day (E-high). After killing, bone mineral measurement, histomorphometry, microdamage analysis, and biomechanical testing were performed. EHDP treatment suppressed intracortical and trabecular remodeling by 60%-75% at the lower dose, and by 100% at the higher dose. Osteoid accumulation caused by a mineralization deficit occurred only in the E-high group, and this led to a reduction of mineralized bone mass. Microdamage accumulation increased significantly by two- to fivefold in the rib, lumbar vertebra, ilium, and thoracic spinous process in E-low, and by twofold in the lumbar vertebra and ilium in E-high. However, no significant increase in damage accumulation was observed in ribs or thoracic spinous processes in E-high where fractures occur following 12 months of treatment. Mechanical properties of lumbar vertebrae and thoracic spinous processes were reduced significantly in both E-low and E-high. These findings suggest that suppression of bone remodeling by EHDP allows microdamage accumulation, but that osteoid accumulation reduces production of microdamage.

Animals↗
PubMed2001

Pain treatment thresholds in children after major surgery.

OBJECTIVE: The objectives of this study were to use a self-report pain scale to examine child pain treatment thresholds after major surgery (i.e., the level of pain they are comfortable with before requiring analgesia), as well as to examine agreement between mother-, nurse-, and child-rated pain treatment thresholds. METHODS: Twenty-five children aged 6 to 16 years were interviewed for 3 consecutive days after major surgery. Subjects used the Faces Pain Scale to rate their current pain, worst postoperative pain, and pain level at which they would like to receive analgesia (the pain treatment threshold). Parents and nurses also estimated the child pain treatment thresholds. RESULTS: For day 1, mean pain was 1.86 of a maximum of 6, mean worst pain was 4.16, and mean pain treatment threshold was 2.28. For day 2, these values were 1.90, 4.10, and 2.54, and for day 3 they were 1.62, 4.56, and 1.85, respectively. Mean scores for all 3 days were as follows: pain, 1.79; worst pain, 4.15; and pain treatment threshold, 2.33. Although mother-nurse ratings were correlated (0.471), mother-child and nurse-child ratings were not significantly correlated. Using the pain treatment threshold as the criterion, 36% of our subjects were undermedicated after the first day of surgery. CONCLUSION: Pain treatment thresholds seem to be lower in children after major as compared with minor surgery. Parents and nurses are not accurate in rating child pain treatment thresholds. Parents tended to overestimate their child's pain treatment threshold, whereas nurses were less consistent in their scoring.

Adolescent↗
PubMed2001

Impact of exercise on bone health and contraindication of oral contraceptive use in young women.

PURPOSE: The effect of quantified resistance and high impact exercise training on bone mass as modified by age and oral contraceptive (OCont) use in young women was studied. METHODS: Women were categorized by age (18-23 vs 24-31 yr) and OCont use, and were then randomized into either three sessions of resistance exercise plus 60 min.wk-1 of jumping rope or a control group for 24 months. Total body, spine, femoral neck, greater trochanter, Ward's area, and radial bone mineral density (BMD) and/or content (BMC), biochemical markers of bone turnover, dietary intake of calcium, lean body mass, maximal oxygen uptake, and strength were determined at baseline and every 6 months. RESULTS: Total body (TB) BMC percent change from baseline was higher in exercisers compared with nonexercisers at 6 and 24 months. OCont users had lower bone turnover at baseline and a decrease in TBBMC from baseline compared with non-OCont users at 24 months. Spine BMC and BMD decreased in the exercise and OCont group at 6 months and remained significantly below nonexercisers who used oral contraceptives at 2 yr. Femoral neck BMD also decreased in the exercise and oral contraceptive group at 6 months. CONCLUSIONS: Exercise prevented a decline in TBBMC seen in the nonexercisers. On the other hand, exercise in oral contraceptive users prevented the increase observed in the spine of the nonexercise plus OCont group.

Adolescent↗
PubMed2001

Effect of long-term exposure to fluoride in drinking water on risks of bone fractures.

Findings on the risk of bone fractures associated with long-term fluoride exposure from drinking water have been contradictory. The purpose of this study was to determine the prevalence of bone fracture, including hip fracture, in six Chinese populations with water fluoride concentrations ranging from 0.25 to 7.97 parts per million (ppm). A total of 8266 male and female subjects > or =50 years of age were enrolled. Parameters evaluated included fluoride exposure, prevalence of bone fractures, demographics, medical history, physical activity, cigarette smoking, and alcohol consumption. The results confirmed that drinking water was the only major source of fluoride exposure in the study populations. A U-shaped pattern was detected for the relationship between the prevalence of bone fracture and water fluoride level. The prevalence of overall bone fracture was lowest in the population of 1.00-1.06 ppm fluoride in drinking water, which was significantly lower (p < 0.05) than that of the groups exposed to water fluoride levels > or =4.32 and < or =0.34 ppm. The prevalence of hip fractures was highest in the group with the highest water fluoride (4.32-7.97 ppm). The value is significantly higher than the population with 1.00-1.06 ppm water fluoride, which had the lowest prevalence rate. It is concluded that long-term fluoride exposure from drinking water containing > or =4.32 ppm increases the risk of overall fractures as well as hip fractures. Water fluoride levels at 1.00-1.06 ppm decrease the risk of overall fractures relative to negligible fluoride in water; however, there does not appear to be similar protective benefits for the risk of hip fractures.

Aged↗
PubMed2001

Genome screen for quantitative trait loci underlying normal variation in femoral structure.

Femoral structure contributes to bone strength at the proximal femur and predicts hip fracture risk independently of bone mass. Quantitative components of femoral structure are highly heritable traits. To identify genetic loci underlying variation in these structural phenotypes, we conducted an autosomal genome screen in 309 white sister pairs. Seven structural variables were measured from femoral radiographs and used in multipoint sib-pair linkage analyses. Three chromosomal regions were identified with significant evidence of linkage (log10 of the odds ratio [LOD] > 3.6) to at least one femoral structure phenotype. The maximum LOD score of 4.3 was obtained for femur neck axis length on chromosome 5q. Evidence of linkage to chromosome 4q was found with both femur neck axis length (LOD = 3.9) and midfemur width (LOD = 3.5). Significant evidence of linkage also was found to chromosome 17q, with a LOD score of 3.6 for femur head width. Two additional chromosomal regions 3q and 19p gave suggestive (LOD > 2.2) evidence of linkage with at least two of the structure phenotypes. Chromosome 3 showed evidence of linkage with pelvic axis length (LOD = 3.1), midfemur width (LOD = 2.8), and femur head width (LOD = 2.3), spanning a broad (60 cm) region of chromosome 3q. Linkage to chromosome 19 was supported by two phenotypes, femur neck axis length (LOD = 2.8) and femur head width (LOD = 2.8). This study is the first genome screen for loci underlying variation in femoral structure and represents an important step toward identifying genes contributing to the risk of osteoporotic hip fracture in the general population.

Adult↗
PubMed2001

Importance of precision in bone density measurements.

Bone densitometry, regardless of the specific technique, is not perfectly reproducible even when consistently performed in exact accordance with the manufacturer's recommendations. Precision must be quantified at each densitometry facility in precision studies of the various skeletal sites used for monitoring. The precision, as the root-mean-square standard deviation or root-mean-square coefficient of variation, is then used to determine the change in bone density that constitutes the least significant change and the minimum interval between follow-up measurements. Until precision studies are performed, the least significant change cannot be determined for any level of statistical confidence, making the interpretation of serial studies impossible.

Absorptiometry, Photon↗
PubMed2000

Pain response in Chinese and non-Chinese Canadian infants: is there a difference?

This study was designed to compare the behavioural pain responses of 2-month-old Canadian-born Chinese babies receiving a routine immunization to those of non-Chinese infants in similar situations. Two groups of 26 infants were obtained from a pediatric clinic held by a Chinese pediatrician and a suburban pediatric practice of a large Canadian city. Facial expression using the Neonatal Facial Coding System (Grunau, R.V.E., Craig, K.D., 1987. Pain expression in neonates: facial action and cry. Pain, 28, 395-410.) and cry using the Fast Fourier Transform were measured during 30 s following the insertion of the needle. Acculturation in Chinese mothers, circadian rhythm, gender, height and weight in infants were assessed. Multivariate analysis of variance revealed significant differences in pain response between these two groups with the Chinese babies showing greater response. No significant effect of circadian rhythm and gender was identified. These results suggest the presence of differences in acute pain response in relation to culture by at least 2 months of age.

Adult↗
PubMed2000

Does suppression of bone turnover impair mechanical properties by allowing microdamage accumulation?

One plausible purpose of bone turnover is to repair bone microdamage. We hypothesized that suppression of bone turnover impairs bone quality by allowing accumulation of microdamage. We investigated the effect of high-dose etidronate (EHDP) on bone's mechanical properties and microdamage accumulation. Skeletally mature beagles, 1-2 years old at the beginning of the study, were treated with daily injections of vehicle or EHDP at 0.5 mg/kg per day or 5.0 mg/kg per day for 1 year. X-rays were taken at baseline and monthly from 7 to 12 months. Bones were taken upon sacrifice and biomechanical tests, histomorphometry, and microdamage analyses were performed. Fractures of ribs and/or thoracic spinous processes were found in 10 of 11 dogs treated with the higher dose EHDP. Only one fracture of a thoracic spinous process was found in dogs treated with the lower dose EHDP, and no fractures were found in the vehicle controls. Biomechanical tests showed reduced mechanical strength in ribs and lumbar vertebrae, but not in the femoral diaphysis or thoracic spinous process in the higher dose EHDP group. Histomorphometric measurements showed a significant reduction of cancellous bone turnover in both EHDP-treated groups compared with controls. In dogs treated with the higher dose EHDP, activation frequency was reduced to zero in both cortical and cancellous bone. Osteoid volume increased significantly, especially in trabecular bone, resulting in reduced mineralized bone volume in the higher dose EHDP group. Microcrack numerical density (Cr.Dn) increased significantly only in the lumbar vertebral body in the higher dose EHDP group, but not in the rib or thoracic spinous process where fractures occurred. These findings show that suppression of bone turnover using high doses of EHDP is associated with fractures of the ribs and spinous processes in dogs. This is most likely the result of excessive amounts of unmineralized bone produced by the inhibition of mineralization at these high doses, rather than by the accumulation of microdamage.

Animals↗
PubMed2000

Sib pair linkage and association studies between bone mineral density and the interleukin-6 gene locus.

A major determinant of the risk for osteoporosis in later life is bone mineral density (BMD) attained during early adulthood. Bone mineral density is a complex trait that, presumably, is influenced by multiple genes. Interleukin-6 (IL-6) is an attractive candidate gene for osteoporosis susceptibility, because it has effects on bone cells and has been implicated in the pathogenesis of osteoporosis. Furthermore, previous investigators have identified an association between a 3' UTR polymorphism of the IL-6 gene and BMD. In this study, we searched for linkage and association between this IL-6 gene polymorphism and peak BMD in a large population (812 individuals) of healthy premenopausal sibpairs. Although previous investigators identified only 6 IL-6 alleles, we identified 17 alleles by modifying electrophoretic conditions and evaluating a very large population. We found no evidence for either linkage or association between the IL-6 gene locus and BMD of the spine or hip in either Caucasians or African Americans.

Adult↗
PubMed2000

Genome screen for QTLs contributing to normal variation in bone mineral density and osteoporosis.

A major determinant of the risk for osteoporosis is peak bone mineral density (BMD), which is largely determined by genetic factors. We recently reported linkage of peak BMD in a large sample of healthy sister pairs to chromosome 11q12-13. To identify additional loci underlying normal variations in peak BMD, we conducted an autosomal genome screen in 429 Caucasian sister pairs. Multipoint LOD scores were computed for BMD at four skeletal sites. Chromosomal regions with LOD scores above 1.85 were further pursued in an expanded sample of 595 sister pairs (464 Caucasians and 131 African-Americans). The highest LOD score attained in the expanded sample was 3.86 at chromosome 1q21-23 with lumbar spine BMD. Chromosome 5q33-35 gave a LOD score of 2.23 with femoral neck BMD. At chromosome 6p11-12, the 464 Caucasian pairs achieved a LOD score of 2.13 with lumbar spine BMD. Markers within the 11q12-13 region continued to support linkage to femoral neck BMD, although the peak LOD score was decreased to 2.16 in the sample of 595 sibling pairs. Our study is the largest genome screen to date for genes underlying variations in peak BMD and represents an important step toward identifying genes contributing to osteoporosis in the general population.

Adult↗
PubMed2000

Effect of calcium or 25OH vitamin D3 dietary supplementation on bone loss at the hip in men and women over the age of 60.

Dietary supplements that prevent bone loss at the hip and that can be applied safely in the elderly are likely to reduce hip fractures. A daily dietary supplement of 750 mg calcium or 15 microg 25OH vitamin D3 on bone loss at the hip and other sites, bone turnover and calcium-regulating hormones were studied over 4 yr in elderly volunteers using a randomized, double-blind, placebo-controlled trial. Bone mineral density (BMD) was measured by dual x-ray absorptiometry and bone structure by radiographs. Calcium biochemistry and bone turnover markers were measured in blood and urine. The 316 women entering the trial had a mean age of 73.7 yr and the 122 men of 75.9 yr. Baseline median calcium intake was 546 mg/day, and median serum 25OH vitamin D3 was 59 nmol/L. On placebo, loss of BMD at total hip was 2% and femoral medulla expansion was 3% over 4 yr. Calcium reduced bone loss, secondary hyperparathyroidism, and bone turnover. 25OH vitamin D3 was intermediate between placebo and calcium. Fracture rates and drop-out rates were similar among groups, and there were no serious adverse events with either supplement. A calcium supplement of 750 mg/day prevents loss of BMD, reduces femoral medullary expansion, secondary hyperparathyroidism, and high bone turnover. A supplement of 15 microg/day 25OH vitamin D3 is less effective, and because its effects are seen only at low calcium intakes, suggests that its beneficial effect is to reverse calcium insufficiency.

Aged↗