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Biomedical subjects

C C Johnston

Publications and source records attributed to C C Johnston.

At least 19 recordsLinked to original sources
PubMed1996

Sex steroids, bone mass, and bone loss. A prospective study of pre-, peri-, and postmenopausal women.

Although bone loss around the time of menopause is driven by estrogen deficiency, the roles of estrogens and androgens in the preservation of skeletal mass at other stages of life are less well understood. To address this issue we studied 231 women between the ages of 32 and 77 with multiple measurements of sex steroids and bone mass over a period of 2-8 yr. In all women bone mass was negatively associated with concentrations of sex-hormone binding globulin, and positively associated with weight. Bone loss occurred from all skeletal sites in peri- and postmenopausal women, but premenopausal women lost bone only from the hip (-0.3%/yr) and had positive rates of change in the radius and spine. Bone loss was significantly associated with lower androgen concentrations in premenopausal women, and with lower estrogens and androgens in peri- and postmenopausal women. Sex steroids are important for the maintenance of skeletal integrity before menopause, and for as long as 20-25 yr afterwards.

Adult↗
PubMed1996

The genetics of proximal femur geometry, distribution of bone mass and bone mineral density.

To estimate genetic effects on femoral neck geometry and the distribution of bone mineral within the proximal femur a cross-sectional twin analysis was carried out at a university hospital that compared correlations in these traits in pairs of mono- and dizygotic female twins. Monozygotic (MZ, n = 51 pairs, age 49.1 +/- 9.3 years) and dizygotic (DZ, n = 26 pairs, age 45.7 +/- 11.3 years) twins were randomly selected from a larger sample of twins previously studied. Measurements of bone mineral density (BMD), femoral neck angles and length, cross-sectional area and moment of interia, the center of mass of the narrowest cross-section of the femoral neck, and BMDs of regions within the femoral neck were made. A summary index of the resistance of the femoral neck to forces experienced in a fall with impact on the greater trochanter (Fall Index, FI) was calculated. MZ pair intraclass correlations (rMZ) were significantly (p < 0.05) different from zero for all bone mass and femoral geometry variables (0.35 < rMZ < 0.82). DZ pair correlations (rDZ) were lower than rMZ for all variables (0.04 < rDZ < 0.52) except femoral neck length (rDZ = 0.38, rMZ = 0.36). After adjustment for BMD of the femoral neck, rMZ was significantly greater than rDZ, yielding high heritability estimates for regional BMDs (0.72 < H2 < 0.78), the center of mass of the femoral neck (H2 = 0.70, -0.04 to 1.43 95% CI) and the resistance of the femoral neck to forces experienced in a fall (FI, H2 = 0.94, 0.06 to 1.85 95% CI), but not for femoral neck length. Adjustments for age did not alter these findings. It is concluded that there are significant familial influences on the distribution of femoral bone mass and on the calculated structural strength of the proximal femur, but not on femoral neck length. If the assumptions of the twin model are correct, this is evidence for genetic factors influencing these traits.

Absorptiometry, Photon↗
PubMed1996

Developmental changes in response to heelstick in preterm infants: a prospective cohort study.

Twenty-eight preterm infants of 28 weeks gestational age were observed four times over eight weeks in order to determine changes in their pain response. Both routine and sham heelstick procedures were used. Physiological (heart rate and oxygen saturations) and behavioural parameters (three upper facial actions) were used as outcomes. The responses to real heelstick were significantly greater than to sham heelstick for heart rate and all facial actions except one at 28 weeks gestational age, but not for oxygen saturation. The magnitude of response to both real and sham heelstick increased over time. Thus, the older the infant, the more robust and recognisable the response. Since even the youngest infants showed a differential response to pain, professionals caring for such infants need to be able to recognize their more subtle pain responses.

Child Development↗
PubMed1995

Identification of patients with low bone mass by single photon absorptiometry and single-energy X-ray absorptiometry.

Single-photon absorptiometry measurements at the radius and calcaneus have been shown in a number of prospective studies to predict the risk of all fractures as well as measurements at the spine or hip. Single-energy X-ray absorptiometry should do as well or better. These methods should be useful in selecting patients for therapy to treat or prevent osteoporosis.

Absorptiometry, Photon↗
PubMed1995

Peak bone mass in young women.

Increasing peak bone mineral density (BMD) or content (BMC) in young women may help to reduce the incidence of osteoporosis. Identifying the age when peak bone content or density is attained is essential to develop strategies aimed at optimizing peak BMD and BMC. Total body bone mineral density (TBBMD) and content (TBBMC) were measured by a dual X-ray absorptiometer in healthy females (n = 247, aged 11-32 years). TBBMD and TBBMC were modeled separately as a nonlinear function of age. By age 22.1 +/- 2.5 years, 99% of peak BMD is attained, and by age 26.2 +/- 3.7 years, 99% of peak BMC is attained. Nonlinear relationships between weight and TBBMD or TBBMC were also modeled. In this model, the influence of several parameters, including age, weight, and height, on BMC and BMD were simultaneously assessed. A model with age and weight described the best fit for TBBMD, whereas age, weight, and height described the best fit for total body TBBMC.

Absorptiometry, Photon↗
PubMed1995

Prevalence of low femoral bone density in older U.S. women from NHANES III.

Data on the number of U.S. women with low femoral bone mineral density (BMD) are currently available only from indirect estimates. We used dual-energy X-ray absorptiometry (DXA) measurements of femoral BMD from phase 1 of the third National Health and Nutrition Examination Survey (NHANES III, 1988-1991) to estimate prevalences of low femoral BMD in women ages 50 years and older using an approach proposed recently by an expert panel of the World Health Organization (WHO). Cutpoints for low BMD were derived from BMD data of 194 non-Hispanic white (NHW) women aged 20-29 years from the NHANES III dataset. The prevalence of older U.S. women with femoral osteopenia (BMD between 1 standard deviation [SD] and 2.5 SD below the mean of young NHW women) ranged from 34-50% in four different femur regions, which corresponds to approximately 12-17 million women. The prevalence with osteoporosis (BMD > 2.5 SD below the mean of young NHW women) ranged from 17-20%, or approximately 6-7 million women. Prevalences were 1.3-2.4 times higher in NHW women than non-Hispanic black women (NHB), and 0.8-1.2 times higher in NHW versus Mexican American (MA) women. The estimated numbers of NHW, NHB, and MA women with osteopenia were 10-15 million, 800,000-1.2 million, and 300,000-400,000, respectively; corresponding figures for osteoporosis were 5-6 million, 200,000-300,000, and 100,000 respectively. Thus, the first data on BMD from a nationally representative sample of older women show a substantial number with low femoral BMD.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1995

Choosing between predictors of fractures.

The identification of those at highest risk of osteoporotic fractures is a clinical goal that requires appropriate statistical comparisons of potential predictors of fractures. This article provides a formal approach of comparing individual predictors (e.g., bone mass at one site vs bone mass at another), or sets of predictors (e.g., bone mass vs other risk factors), and contrasts newer methods, such as bootstrapping, to receiver-operating-characteristics (ROC) curves, which have been previously used. The advantages of the bootstrapping approach are illustrated using time-to-fracture data from a published study demonstrating the use of baseline bone mass measurements in the prediction of fractures in 521 subjects with variable lengths of follow-up, extending to 12.5 years. Bone mineral density (BMD) was shown to be significantly better than bone mineral content (BMD) in predicting fractures in free-living subjects, but not in retirement-community subjects. Bone mineral apparent density (BMAD) was also compared with BMC and BMD and shown not to improve fracture prediction in these subjects.

Bone Density↗
PubMed1995

Better discrimination of hip fracture using bone density, geometry and architecture.

Bone density predicts the risk of hip fracture. Because hip strength is determined by bone geometry and architecture as well as density, we tested which variables in geometry and architecture were independent discriminators of hip fracture and, if combined with density, improved the discrimination of fracture from non-fracture over bone density alone. The design was a case-control study. The subjects were Caucasian women over the age of 60 years who had sustained a hip fracture after the age of 58 years (n = 22), and controls matched for age and weight (n = 43) and unmatched controls (n = 317) with no history of hip fracture. Variables in density, geometry and architecture were obtained from dual-energy X-ray absorptiometry images and from radiographs of the upper end of the femur. In a univariate model, of the measures of bone mass, the best discriminator of hip fracture was bone mineral density of the neck of femur; of the geometric measurements, it was hip axis length; and of the measurements of bone architecture, it was Singh grade. In a multivariate model, these three variables were shown to be independent discriminators of hip fracture. When hip axis length was combined with bone mineral density, there was significant improvement in discrimination of hip fracture (p = 0.014), and when Singh grade was combined with hip axis length and bone mineral density there was a further significant improvement (p = 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1995

Pathogenesis of osteoporosis.

Fractures, the clinical outcome associated with osteoporosis, have a complex pathogenesis involving, in most cases, both trauma to the bone and increased skeletal fragility. Recent evidence also suggests that the geometry of the bone is important in determining fracture risk, and geometric properties are in part genetically determined. Skeletal fragility is largely determined by bone mass and the microstructure of bone. Loss of trabeculae and their connections has been well documented and undoubtedly contributes to risk of some fractures. Microdamage has also been shown to occur within the skeleton and could contribute to fragility. Peak bone mass is a major factor in determination of subsequent fracture risk and it has both genetic and environmental determinants. Twin studies have suggested a major genetic contribution and that a few genes may be responsible, but these genes have not been clearly identified. Nutrition, especially calcium intake, and exercise also contribute to the determination of peak bone mass and are especially important during the major period of bone acquisition up to the age of 18. Bone loss among women begins in the perimenopausal period, although loss from the hip begins earlier. The loss is associated with both estrogen and androgen concentrations. Later in life other factors such as the development of secondary hyperparathyroidism may contribute to the continued loss of bone. Males lose bone at about half the rate of females, but the underlying contributing factors are not well documented. The pathogenesis of osteoporotic fractures is complex, but this allows for the development of multiple interventions, which may reduce the frequency of such fractures.

Adult↗
PubMed1994

Do variations in hip geometry explain differences in hip fracture risk between Japanese and white Americans?

Despite lower femoral neck bone mass, Japanese women have a substantially lower incidence of hip fracture than North American whites. Reasons for this discrepancy were sought in a study of 57 Japanese and 119 white American women aged 50-79. All women were in good health. Bone mineral content (BMC) in the femoral neck, femoral neck length (NL), femoral neck angle (theta), cross-sectional moment of inertia (CSMI), safety factor (SF), and fall index (FI) were calculated using dual x-ray absorptiometry. Height and weight were greater in Americans than in Japanese (1.62 versus 1.52 m; p < 0.0001 and 66.0 versus 49.4 kg; p < 0.0001, respectively). Mean BMC in the femoral neck and CSMI were greater in Americans than in Japanese (3.91 versus 3.02 g; p < 0.0001 and 0.99 versus 0.57 cm4; p < 0.0001, respectively). NL was longer in Americans (5.6 versus 4.4 cm; p < 0.0001) and theta was larger in Americans (130 versus 128 degrees; p < 0.01), whereas SF and FI were less in Americans than in Japanese (3.41 versus 5.12; p < 0.0001 and 1.00 versus 1.40; p < 0.0001, respectively). These results indicate that despite lower bone mass, Japanese women have lower risks of structural failure in the femoral neck, attributable primarily to shorter femoral necks and, to a lesser degree, a smaller femoral neck angle. Geometric characteristics of the femoral neck in Japanese women are associated with their lower hip fracture risk, and the measurement of proximal femoral geometry, combined with bone mass, may provide further clinical information about the risk of hip fracture.

Absorptiometry, Photon↗
PubMed1994

Peak bone mass, bone loss and risk of fracture.

Both peak bone mass and bone loss contribute to subsequent fracture risk. Other variables such as architectural abnormalities, microdamage, geometric properties, and trauma probably contribute as well. Until the contribution of these other potentially important risk factors can be quantified, it will be difficult to determine precisely the relative importance of peak bone mass and subsequent bone loss in the etiology of fractures.

Bone Density↗
PubMed1994

Influences on skeletal mineralization in children and adolescents: evidence for varying effects of sexual maturation and physical activity.

OBJECTIVE: To establish rates of skeletal mineralization in children and adolescents, and to identify factors that influence these rates. DESIGN: Three-year observational study. SETTING: University hospital. SUBJECTS: Ninety white children, aged 6 to 14 years. MEASUREMENTS: Bone mineral density of the radius, spine, and hip was measured at baseline and 3 years later. Physical activity was assessed by questionnaires at 6-month intervals and dietary calcium intake by diet diary 1 day per month for 36 months. Sexual maturation (Tanner stage) was determined by an endocrinologist at 6-month intervals, as necessary to classify children as prepubertal, peripubertal, or postpubertal. RESULTS: Skeletal mineralization accelerated markedly at puberty in the spine (0.077 vs 0.027 gm/cm2 per year, peripubertal vs prepubertal) and greater trochanter (0.050 vs 0.027 gm/cm2 per year), less markedly in the femoral neck (0.047 vs 0.030 gm/cm2 per year), and only slightly in the radius. Nearly one third (15 gm) of the total skeletal mineral in the lumbar spine of adult women (approximately 52 gm) was accumulated in the 3 years around the onset of puberty. Increases in height and weight were the strongest correlates of skeletal mineralization: weight changes were more strongly correlated with trabecular bone sites and changes in height with cortical bone sites. Increases in calf muscle area were strongly associated with mineralization, particularly in peripubertal children, and physical activity was associated with more rapid mineralization in prepubertal children. CONCLUSIONS: Puberty has varying effects on skeletal mineralization depending on skeletal site; trabecular bone is apparently more sensitive to changing hormone concentrations. Physical activity and normal growth are also positively associated with skeletal mineralization, also depending on skeletal site and sexual maturation.

Adolescent↗
PubMed1994

Judging pain in newborns: facial and cry determinants.

Explored the facial and cry characteristics that adults use when judging an infant's pain. Sixteen women viewed videotaped reactions of 36 newborns subjected to noninvasive thigh rubs and vitamin K injections in the course of routine care and rated discomfort. The group mean interrater reliability was high. Detailed descriptions of the infants' facial reactions and cry sounds permitted specification of the determinants of distress judgments. Several facial variables (a brow bulge, eyes squeezed shut, and deepened nasolabial fold constellation, and taut tongue) accounted for 49% of the variance in ratings of affective discomfort after controlling for ratings of discomfort during a noninvasive event. In a separate analysis not including facial activity, several cry variables (formant frequency, latency to cry) also accounted for variance (38%) in ratings. When the facial and cry variables were considered together, cry variables added little to the prediction of ratings in comparison to facial variables. Cry would seem to command attention, but facial activity, rather than cry, can account for the major variations in adults' judgments of neonatal pain.

Adolescent↗
PubMed1994

Bone mineral density in relation to polymorphism at the vitamin D receptor gene locus.

Polymorphism at the vitamin D receptor gene was examined in relation to bone mineral density (BMD) at spine, femur, and forearm in 86 monozygotic (MZ) and 39 dizygotic (DZ) adult female twins. All were white, 63 pairs (44 MZ, 19 DZ) were premenopausal, and 43 pairs (31 MZ, 12 DZ) were discordant for age at menopause or use of estrogen. Each individual of the DZ pairs and one individual of MZ pairs was genotyped for ApaI, BsmI, and TaqI polymorphism at the vitamin D receptor gene locus using Southern hybridization. Intraclass correlations for BMD in MZ and DZ twin pairs indicated that heritability accounted for over 70% of BMD. There was no relationship between genotype for any of the three polymorphisms and BMD at any skeletal site in the twin population, considered either as a total population, both with and without twins discordant for age at menopause or use of estrogen, or as a premenopausal population. In DZ twin pairs discordant for alleles for the three polymorphisms, no allele was associated with higher or lower BMD. It is concluded that in this population of healthy adult females there was no relationship between these polymorphisms at the vitamin D receptor gene locus and BMD.

Adult↗
PubMed1993

Risk assessment: theoretical considerations.

Measurements of bone mass and several other skeletal characteristics can effectively identify women at high risk for fractures. These measurements are now widely available, and other clinical data cannot provide equivalent information. Treatments exist that will preserve bone mass and presumably reduce fracture risk (although for newer treatments this requires further study). It should also be noted that the prevention of very rapid bone loss may also protect against the development of micro-architectural abnormalities, thereby further reducing risk. Even in the very old, for whom preservation of bone mass may be of less value, there now appears to be an intervention that diminishes the impact trauma associated with falls. In this group bone mass measurements may also aid in identification of the highest risk groups. It is worth noting that measurement of bone mass may further serve to motivate patients to accept or to continue with a therapy.

Absorptiometry, Photon↗