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Biomedical subjects

C C Johnston

Publications and source records attributed to C C Johnston.

At least 37 records · Page 2Linked to original sources
PubMed2000

Suppressed bone turnover by bisphosphonates increases microdamage accumulation and reduces some biomechanical properties in dog rib.

It has been hypothesized that suppression of bone remodeling allows microdamage to accumulate, leading to increased bone fragility. This study evaluated the effects of reduced bone turnover produced by bisphosphonates on microdamage accumulation and biomechanical properties of cortical bone in the dog rib. Thirty-six female beagles, 1-2 years old, were divided into three groups. The control group (CNT) was treated daily for 12 months with saline vehicle. The remaining two groups were treated daily with risedronate (RIS) at a dose of 0.5 mg/kg per day or alendronate (ALN) at 1.0 mg/kg per day orally. After sacrifice, the right ninth rib was assigned to cortical histomorphometry or microdamage analysis. The left ninth rib was tested to failure in three-point bending. Total cross-sectional bone area was significantly increased in both RIS and ALN compared with CNT, whereas cortical area did not differ significantly among groups. One-year treatment with RIS or ALN significantly suppressed intracortical remodeling (RIS, 53%; ALN, 68%) without impairment of mineralization and significantly increased microdamage accumulation in both RIS (155%) and ALN (322%) compared with CNT. Although bone strength and stiffness were not significantly affected by the treatments, bone toughness declined significantly in ALN (20%). Regression analysis showed a significant nonlinear relationship between suppressed intracortical bone remodeling and microdamage accumulation as well as a significant linear relationship between microdamage accumulation and reduced toughness. This study showed that suppression of bone turnover by high doses of bisphosphonates is associated with microdamage accumulation and reduced some mechanical properties of bone.

Alendronate↗
PubMed1999

Rates of growth and loss of bone mineral in the spine and femoral neck in white females.

This study characterizes the rates of growth and loss of bone mass as a function of age in white females. It combines longitudinal data from several studies of bone mass on healthy white female subjects ranging from age 6 to 90 years. Rates of change in bone area, bone mineral content (BMC) and bone mineral density (BMD) are estimated separately for the spine and the femoral neck of each individual using linear regression. The individual rates of change are then fitted as a nonparametric function of age using weighted moving averages, resulting in a curve of age-specific mean change as a function of age. When the curves of BMD were compared between the hip and the femoral neck, the cessation of bone growth and the onset of bone loss were found to occur at an earlier age at the hip than at the spine. No significant differences in the ages of maximum rates of growth or maximum loss were found between the two skeletal sites. This information will be useful for designing interventions to promote bone growth or retard bone loss.

Adolescent↗
PubMed1999

Polymorphism at an Sp1 binding site of COL1A1 and bone mineral density in premenopausal female twins and elderly fracture patients.

Polymorphism at an Sp1 binding site in the COL1A1 gene has been reported to be associated with bone mineral density (BMD) and osteoporotic vertebral fracture. We therefore examined for associations and linkage of the Sp1 polymorphism in the COL1A1 gene and BMD at the lumbar spine and femoral neck in 38 monozygotic (MZ) and 40 dizygotic (DZ) twin pairs of white adult women. All twins were premenopausal with an age range of 21-49 years. Sp1 genotypes of 56 patients with idiopathic osteoporotic vertebral fracture were examined for a preponderance of either genotype relative to our normal healthy twin subjects. In the twin sample no significant association was found between Sp1 genotypes and BMD at the spine and femoral neck. No linkage of Sp1 genotype and BMD at the spine or femoral neck was observed in DZ twins discordant for genotype. Frequencies of Sp1 genotypes were similar in our healthy (twin) and fracture population samples. In conclusion, in our American sample of premenopausal twins we found no association or linkage of the Sp1 polymorphism at the COL1A1 gene and BMD at the lumbar spine and femoral neck, and no over-representation of any Sp1 genotype was observed in our sample of patients with osteoporotic vertebral fracture. Taken together these results indicate that the Sp1 polymorphism is not related to BMD in our American sample, and contrasts with the findings in a British population.

Adult↗
PubMed1999

Risedronate, a highly effective, short-term oral treatment for Paget's disease: a dose-response study.

Risedronate is a potent pyridinyl bisphosphonate being developed for bone diseases such as Paget's disease and osteoporosis. In this study, we compared the efficacy, safety, and tolerability of three different doses of oral risedronate in 62 patients with severe Paget's disease of bone [serum alkaline phosphatase (AP) >3 times the upper limit of normal]. Patients were treated at six study centers with either 10, 20, or 30 mg oral risedronate daily for 28 days and followed up to day 85. The primary efficacy parameter was percentage change from baseline in AP excess. The data show that there is a dose-response with risedronate: patients who received 30 mg oral risedronate for 28 days benefited most, with a mean percentage decrease in AP excess of 72.2% (20 mg: 57.9%; 10 mg: 48. 0%). Time to response-the first time point when there was a >/=30% reduction from baseline in AP excess and >/=50% reduction from baseline in urinary hydroxyproline (HP)/creatinine-was also significantly shorter (median 29 days) in the 30 mg group compared with the other two groups (20 mg: 43 days and 10 mg: 71 days). Long-term follow-up data up to 33 months from the start of the study indicated that AP remained below baseline levels for all patients. Histologic evaluation of bone formed during risedronate therapy demonstrated that normal lamellar bone was formed as opposed to woven pagetic bone, with no evidence of osteomalacia. Risedronate was well tolerated. Transient decreases in serum calcium and increases in serum intact parathyroid hormone were observed, consistent with the pharmacology of risedronate. In conclusion, risedronate administered at daily doses of 10, 20, and 30 mg for 28 days was effective in reducing the biochemical indices of disease activity in patients with severe Paget's disease of bone. A daily dose of 30 mg was most effective without compromising safety or tolerability.

Administration, Oral↗
PubMed1999

Previous milk consumption is associated with greater bone density in young women.

BACKGROUND: Dietary calcium and milk intakes at specific ages may influence bone mineral measures at specific sites during development of peak bone mass. OBJECTIVE: Relations of previous milk intake and current calcium intake to current bone mineral measures were investigated in young women. DESIGN: A food-frequency interview and recall of previous milk intake from early childhood to 12 y of age and during adolescence (13-19 y) were completed in a cross-sectional analysis in young women (age 18-31 y; n = 224). Three levels of previous milk intake were defined: 1) infrequently or never, 2) sometimes, and 3) at every or almost every meal. Total body (TB), femoral neck, radius (R), and spine (S) bone mineral density (BMD) and bone mineral content (BMC) were determined by using dual-energy X-ray absorptiometry. RESULTS: Childhood and adolescent milk intakes were positively correlated (r = 0.66). Childhood and adolescent milk intakes correlated with current calcium intakes (r = 0.26 and 0.33, respectively). Adolescent milk intake correlated with RBMD (r = 0.16). When weight was controlled for, adolescent milk intake correlated with TBBMD (r = 0.16), TBBMC (r = 0.21), SBMC (r = 0.16), RBMD (r = 0.18), and RBMC (r = 0.15). Current calcium intakes correlated with SBMC (r = 0.17). Regression analyses supported these results. CONCLUSIONS: Results were consistent with the hypothesis that higher milk intake during adolescence is associated with greater total body, spine, and radial bone mineral measures during development of peak bone mass, whereas current calcium intakes may influence SBMC. In addition, milk intake at a younger age may contribute to similar habits of milk intake later in life.

Adolescent↗
PubMed1999

Effect of repeated doses of sucrose during heel stick procedure in preterm neonates.

The purpose of this randomized clinical trial was to test the efficacy of repeated versus single dose sucrose to decrease pain from routine heel stick procedures in preterm neonates. Infants (n = 48) in the first week of life with a mean gestational age of 31 weeks received 0.05 ml of 24% sucrose solution or sterile water by mouth (1) 2 min prior to actual lancing of the heel; (2) just prior to lancing, and (3) 2 min after lancing. The single-dose group received sucrose for the first dose and water for the second and third dose; the repeated-dose group received sucrose three times, and the placebo group received only water. The Premature Infant Pain Profile (PIPP) scores were obtained for five 30-second blocks from lancing. Both sucrose groups had lower PIPP scores (single sucrose pain scores, 6.8-8.2, p = 0.07; repeated sucrose pain scores, 5.3-6. 2, p < 0.01) than water (pain scores 7.9-9.1), and in the last block, the repeated dose had lower scores than the single dose (6.2 vs. 8. 2, p < 0.05).

Analgesics↗
PubMed1999

Do cry features reflect pain intensity in preterm neonates? A preliminary study.

The purpose of this study was to investigate if cries from preterm neonates would reflect changes in pain intensity following interventions. The cries from 25 preterm neonates from an original sample of 122 were audiorecorded while the infant was undergoing heelstick during a randomized crossover design testing the efficacy of: pacifier with sucrose or water, or prone position as compared to standard care. Both pacifier conditions reduced procedural pain according to a validated composite pain measure (the Premature Infant Pain Profile). There were proportionately fewer cries in the two pacifier groups compared to the prone positioning and standard care groups, and cry duration was positively correlated with PIPP scores. However, neither cry duration nor fundamental frequency reflected group differences. Further research is needed to determine if cry is a sensitive and valid indicator of pain in preterm infants.

Blood Specimen Collection↗
PubMed1999

Sibling pair linkage and association studies between bone mineral density and the insulin-like growth factor I gene locus.

A major determinant of the risk for osteoporosis in later life is bone mineral density (BMD) attained during early adulthood. BMD is a complex trait that presumably is influenced by multiple genes. Insulin-like growth factor I (IGF-I) is an attractive candidate gene for osteoporosis susceptibility, because IGF-I has marked effects on bone cells and has been implicated in the pathogenesis of osteoporosis. The IGF-I gene contains a microsatellite repeat polymorphism approximately 1 kb upstream from the IGF-I gene transcription start site, and previous investigators have found a higher prevalence of the 192/192 genotype of this polymorphism among men with idiopathic osteoporosis compared to controls. In this study we used this IGF-I polymorphism to test for an association between this polymorphism and BMD in our large population of premenopausal women (1 sister randomly chosen from 292 Caucasian and 71 African-American families). We also used this polymorphism to detect linkage to BMD elsewhere in the IGF-I gene or in a nearby gene using sibling pair linkage analysis in healthy premenopausal sister pairs (542 sibling pairs: 418 Caucasian and 124 African-American). Neither test provided any evidence of linkage or association between the IGF-I gene locus and spine or femoral neck BMD in Caucasians or African-Americans.

Adult↗
PubMed1998

Bone mass and structure at the hip in men and women over the age of 60 years.

Bone mass and structure at the proximal femur are important predictors of hip fracture. The aims of this study were to compare in a large sample of elderly men and women the precision of measurements of bone mass and structure at multiple sites at the proximal femur, to examine their interrelationships, to establish their relationships with age and body size, and to examine criteria for defining geometric and architectural variables in bone structure. Women (n = 336) and men (n = 141) over the age of 60 years were studied cross-sectionally. Bone mineral density (BMD) and content (BMC) at the proximal femur were measured in duplicate by dual-energy X-ray absorptiometry (DXA). Shaft and total upper femur (hip) sites in addition to femoral neck, Ward's triangle and trochanter were measured. Structural variables, measured from radiographs and from DXA images, including cortical thickness at calcar femorale, lateral cotex and midfemur, width of the femur and medulla, Singh grade, hip and femoral axis length, femoral head and neck width and the center of mass of the femoral neck. BMD and BMC had high reproducibility and there were significant differences in reproducibility across sites. Among sites, total upper femur and shaft had the highest reproducibility. Duplicate measurements substantially improved reliability of the measurement and are recommended when the value is close to a diagnostic level or when it will be used to establish rates of change. Reproducibility of structural variables was also high except for the lateral cortex, center of mass and Singh grade. Variance due to measurement error did not change with either age or gender. Women were significantly different from men, after controlling for differences in body size, in all variables except Singh grade and medulla width. BMD and BMC were negatively related to age and positively to body size. Structural variables examined in relation to age and body size fell into two categories. The first comprised variables that were not age-related but were body-size-related suggesting that they could be classified as geometric variables. The second comprised variables that were both body-size-related and age-related, suggesting that they could be classified as architectural variables. Using these criteria, calcar and lateral cortex were architectural variables, whereas shaft width, hip and femoral axis length, femoral head and neck width, and center of mass were geometric in both men and women. In women, shaft cortex width and medulla width were age-related, whereas in men they were not. Singh grade showed no consistent pattern with age or body size in women and men.

Absorptiometry, Photon↗
PubMed1998

Updated data on proximal femur bone mineral levels of US adults.

This paper describes data on bone mineral levels in the proximal femur of US adults based on the nationally representative sample examined during both phases of the third National Health and Nutrition Examination Survey (NHANES III, 1988-94), and updates data previously presented from phase 1 only. The data were collected from 14,646 men and women aged 20 years and older using dual-energy X-ray absorptiometry, and included bone mineral density (BMD), bone mineral content (BMC) and area of bone scanned in four selected regions of interest (ROI) in the proximal femur: femur neck, trochanter, intertrochanter and total. These variables are provided separately by age and sex for non-Hispanic whites (NHW), non-Hispanic blacks (NHB) and Mexican Americans (MA). NHW in the southern United States had slightly lower BMD levels than NHW in other US regions, but these differences were not sufficiently large to prevent pooling of the data. The updated data provide valuable reference data on femur bone mineral levels of noninstitutionalized adults. The updated data on BMD for the total femur ROI of NHW have been selected as the reference database for femur standardization efforts by the International Committee on Standards in Bone Measurements.

Absorptiometry, Photon↗
PubMed1998

Dietary calcium, protein, and phosphorus are related to bone mineral density and content in young women.

BACKGROUND: Dietary factors have been implicated in modifying bone health, although the results remain controversial, particularly in young women. OBJECTIVE: The objective of the study was to determine relations of selected dietary factors and anthropometric measurements to bone mineral density (BMD) of the spine, femoral neck, trochanter, Ward's triangle, radius, and total body and the bone mineral content (BMC) of the spine, radius, and total body. DESIGN: The study was a cross-sectional analysis of 215 women aged 18-31 y. RESULTS: Weight, height, and lean mass were correlated with bone mineral measures at every site (r = 0.17-0.78). Postmenarcheal age (years since onset of menses) was positively correlated with total-body BMD and BMC, radius BMD and BMC, and spine BMC, and negatively correlated with Ward's triangle BMD. Radius BMD was correlated with protein, calcium, and phosphorus intakes, and spine BMD and BMC were correlated with energy, protein, calcium, and phosphorus intakes. These correlations remained significant when postmenarcheal age, lean mass, and fat mass were controlled. A pattern emerged in multiple regression analyses that showed a complex relation among calcium, protein or phosphorus, and the calcium-protein or calcium-phosphorus ratio and spine or total-body BMC and BMD. All 3 variables (calcium, protein or phosphorus, and calcium-protein or calcium-phosphorus ratio) were required in the model for significance. CONCLUSIONS: Anthropometric measures were predictors of bone mass. A single ratio of calcium to phosphorus or protein did not optimize bone mass across the range of calcium intakes.

Adolescent↗
PubMed1998

Risedronate increases bone mass in an early postmenopausal population: two years of treatment plus one year of follow-up.

This double-blind, placebo-controlled study was undertaken to determine 1) the efficacy of oral risedronate for prevention of bone loss in healthy, early postmenopausal patients with normal bone mass, 2) the effect on bone mass when treatment was stopped, and 3) the safety and tolerance of risedronate in this population. A group of 111 patients were randomized to oral placebo, risedronate 5 mg daily, or risedronate 5 mg cyclically, for 2 yr followed by 1 yr off treatment. Measurements included percentage change from baseline in lumbar spine bone mineral density (BMD) at 24 months; percentage change from baseline in BMD of the femoral neck, trochanteric region, and Ward's triangle region of the proximal femur; and changes in biochemical markers of bone turnover. After 2 yr, there was a mean increase in BMD of the lumbar spine of 1.4% from baseline and of 5.7% vs. placebo in the risedronate 5 mg daily group. There were decreases from baseline in BMD of 1.6% and 4.3% in the risedronate 5 mg cyclic and placebo groups, respectively. By the end of 24 months, trochanteric bone mass at the hip increased by 5.4% in the risedronate 5 mg daily group and by 3.3% in the risedronate 5 mg cyclic group vs. placebo. Bone mass was maintained at the femoral neck in the 2 active-treatment groups vs. a 2.4% mean loss with placebo. During the treatment-free follow-up, bone turnover increased toward baseline in both risedronate groups. By the end of that year, lumbar spine bone mass in all 3 groups was lower than at baseline. Oral risedronate was well tolerated. We conclude that risedronate (5 mg daily) increases bone mass and risedronate (5 mg cyclic) appears to prevent bone loss in early postmenopausal women with normal BMD.

Adult↗
PubMed1998

Linkage of a QTL contributing to normal variation in bone mineral density to chromosome 11q12-13.

Osteoporosis is a leading public health problem that is responsible for substantial morbidity and mortality. A major determinant of the risk for osteoporosis in later life is bone mineral density (BMD) attained during early adulthood. BMD is a complex trait that presumably is influenced by multiple genes. Recent linkage of three Mendelian BMD-related phenotypes, autosomal dominant high bone mass, autosomal recessive osteoporosis-pseudoglioma, and autosomal recessive osteopetrosis to chromosome 11q12-13 led us to evaluate this region to determine if the underlying gene(s) could also contribute to variation in BMD in the normal population. We performed a linkage study in a sample of 835 premenopausal Caucasian and African-American sisters to identify genes underlying BMD variation. A maximum multipoint LOD score of 3.50 with femoral neck BMD was obtained near the marker D11S987, in the same chromosomal region as the three Mendelian traits mentioned above. Our results suggest that the gene(s) underlying these Mendelian phenotypes also play a role in determining peak BMD in the normal population and are the first using linkage methods to establish a chromosomal location for a gene important in determining peak BMD. These findings support the hypothesis that a gene responsible for one or more of the rare Mendelian BMD traits linked to chromosome 11q12-13 has an important role in osteoporosis in the general population.

Adult↗
PubMed1998

Risedronate in the treatment of Paget's disease of bone: an open label, multicenter study.

An open-label, multicenter study was conducted to determine the efficacy and safety of oral risedronate (a pyridinyl bisphosphonate) in 162 patients (102 men, 60 postmenopausal women; mean age, 68 years) with moderate to severe Paget's disease of bone (mean serum alkaline phosphatase [ALP] approximately seven times the upper limit of normal). Patients were treated with oral risedronate, 30 mg/day for 84 days, followed by 112 days without treatment. This 196-day cycle was repeated once if serum ALP did not normalize or increased from the nadir value by > or = 25%. At the end of the first and second cycles, the mean percentage decreases for serum ALP were 65.7% and 69.1%, and for urinary hydroxyproline/creatinine 50.4% and 66.9%, respectively. The decreases from baseline in ALP and urinary hydroxyproline/creatinine were significant (p < 0.001). Normalization of serum ALP was observed in 86 patients (53.8%): 53 during the first treatment cycle and 33 during the second. There was a significant proportion of patients reporting a decrease in the pagetic bone pain at days 84 and 196 (p < 0.001). Overall, risedronate was well tolerated. Five patients withdrew due to adverse events, none of which were considered to be drug related. In conclusion, 30 mg of oral risedronate administered daily for 84 days significantly reduced the biochemical indices of disease activity and was associated with pain reduction in patients with moderate to severe Paget's disease of bone. Normalization of ALP was observed in the majority of patients. Repeated administration of risedronate was shown to be beneficial. In general, risedronate was well tolerated and demonstrated a good safety profile.

Administration, Oral↗
PubMed1998

The challenges of peripheral bone density testing: which patients need additional central density skeletal measurements?

Lower cost, portable, peripheral bone mass measurement devices are being increasingly utilized for widespread bone mass testing. These devices are being placed in traditional medical settings as well as nontraditional settings, such as pharmacies and grocery stores. Increased bone mass testing is appropriate at menopause in women who are undecided whether to begin systemic estrogen replacement. Women may decide to begin estrogen replacement if they are aware they have low bone mass and understand that bone mass will predictably decline after the menopause (1). With the approval of alendronate and raloxifene for the prevention of osteoporosis, even women who cannot or will not utilize estrogen replacement may be offered preventive interventions if they are identified as having low bone mass. More accessible bone mass measurements and more approved pharmacologic interventions will shift the focus of osteoporosis management to strategies that emphasize the reduction of lifetime fracture risk as well as current fracture risk. It will also be an impetus to focus on earlier identification and intervention (2-4).

Journal Article↗