Effects of a new positioner on the precision of hip bone mineral density measurements

In an attempt to reduce patient positioning errors, the authors tested the use of a new hip-specific positioning tool, OsteoDyne's Hip Positioner System (HPS). The HPS is an "A" frame splint designed to abduct both legs approximately 15 degrees to hold them in full extension at the hips and knees and to lock the feet in a neutral position. Seventy volunteer women aged 35-82 years were randomly assigned in two age-matched groups (mean age 56 years). Each group underwent two consecutive femur dual X-ray absorptiometry (DXA) scans with intermediate repositioning using the HPS system and two others utilizing the standard hip positioner provided with Hologic and Lunar scanners. One technician performed all scans using a Hologic QDR 1000-Plus and Lunar DPX-Plus densitometer. One hundred and fifty volunteer women aged 50-84 years (mean age, 64 years) were recruited in a multicenter study for the assessment of precision. Each subject underwent three consecutive femur DXA scans with intermediate repositioning using the HPS system. The coefficient of variation (CV) was significantly improved at the femoral neck by the use of the HPS with 0.7 versus 1.2 with the Hologic densitometer but only moderately altered at other sites. Similar results were found with the Lunar densitometer with improvement of precision at the femoral neck, 0.8 versus 1.8 with a similar trend but no significant difference at the other regions. No statistical difference was noted between the femoral neck BMD measured with the HPS system and with the standard positioners in either group. The mean precision of data obtained on the QDR 1000+ was 0.8% (range 0.1-1.4) for the femoral neck BMD, 1.1% (range 0.1-3.0) for the trochanter BMD, 2.3% (range 0.2-5.2) for Ward's triangle BMD, and 0.8% (range 0.1-1.9) for the total femur BMD. The mean precision of data obtained on the QDR 2000 was 0.7% (range 0.1-2), 1% (range 0.1-4.9), 2.6% (range 0.3-5.7), and 0.7% (range 0.1-1.8), respectively. In conclusion, data obtained with the new OsteoDyne's HPS seem capable of reducing patient positioning errors for the hip measurement. Its use is likely to improve confidence in hip bone mineral density measurements.     

Spinal and femoral bone mass accumulation during normal adolescence: comparison with female patients with sexual precocity and with hypogonadism

Since the attainment of higher bone mineral density (BMD) is a crucial strategy in preventing age-related bone loss and consequent fracture, we determined when bone mass of the lumbar spine (L2-L4) (g/cm2) and femoral neck (g/cm2) reaches its peak in healthy Japanese subjects and examined the influence of early exposure to estrogen and estrogen deficiency on BMD. We also determined the volumetric BMD, termed bone mineral apparent density (BMAD), of the lumbar spine and femoral neck. Using dual-energy x-ray absorptiometry (DXA) (Hologic QDR-1000), we measured BMD of both the lumbar spine and the femoral neck in 31 healthy children aged 2-11 yr, 269 children (138 males and 131 females) aged 13-19 yr, 12 men and 12 women aged 20-34 yr as adult controls, 11 patients with female central sexual precocity, and 3 patients with female primary hypogonadism. Because the densitometric data obtained from DXA are strongly influenced by the size of the bone in growing subjects, the volumetric BMAD (g/cm3) of the vertebral cube (L2-L4) and femoral neck were determined: BMAD (g/cm3) = BMD (g/cm2)/square root of scanned area (cm2) for the lumbar spine and by BMAD = BMD/width for the femoral neck. The BMD, both lumbar spine and femoral neck, nearly reached its peak at age 14.5-15 yr in girls and 16.5-17 yr in boys when compared with adult normal values. The difference in this age between sexes is identical to the difference in age at sexual maturation. BMD in patients with sexual precocity was high compared to age-matched controls, whereas patients with primary hypogonadism showed lower lumbar apparent BMD, and the increase in lumbar BMAD (g/cm3) was noted after the progression of puberty in healthy children, probably suggesting the importance of sex steroids in the increase of BMD and lumbar BMAD in both sexes. The girls with earlier menarche showed higher lumbar BMD at age 18 and 19 yr. For the femoral BMAD, there was no significant relationship between this value and age in girls. We conclude that peak bone mass is mainly achieved by late adolescence in Japanese as in Caucasians and that pubertal progression and probably estrogen itself play a crucial role in accumulation of bone mass in females.     

Screening for osteopenia and osteoporosis: do the accepted normal ranges lead to overdiagnosis?

Osteoporosis is a common disease which causes significant morbidity and mortality and in many cases may be preventable. In the absence of fragility fractures the accepted method of identifying those at high risk is based upon bone mineral density (BMD) measurements with defined cut-off points. To correctly delineate normal from abnormal, reliable reference ranges appropriate to the observed population are required. We have studied the age-dependent changes in mean BMD and standard deviation at the lumbar spine and femoral neck in a normal population extracted from 4280 women screened for osteopenia and compared our findings with the manufacturer's normal range (MNR). The recent World Health Organization criteria for the diagnosis of osteopenia and osteoporosis using the 'manufacturer's young normal' (MYN) values and our 'study young normal' (SYN) values have been applied. The study normal population (SNP) included 2068 women (mixed social class; mean age 53 years, range 30-79 years). The distribution of mean lumbar spine BMD with age in SNP was generally similar to the MNR. In contrast mean femoral neck bone density from SNP was significantly different from the MNR, ranging from 3% to 12% lower in each 5-year group analysed (p < 0.05). Comparison of standard deviations in spine BMD in SNP against the fixed MNR standard deviation showed a statistically significant increase commencing at 45 years of age. The magnitude of this increase appeared to rise with age and remained significant in the 75- to 79-year age group (p < 0.05). In contrast, standard deviation in femoral neck BMD in SNP appeared relatively constant with age except in the group of women at and around the time of the menopause. The SYN value for mean lumbar spine BMD was 0.994 g/cm2 (cf. MYN value 1.047, p < 0.0001) with a standard deviation of 0.122 g/cm2 (cf. MYN 0.11, p = 0.0005). Similarly our SYN value for femoral neck BMD was 0.787 (cf. MYN value 0.895, p < 0.0001) with a standard deviation of 0.109 (cf. MYN value 0.10, p = 0.0027). Using SYN values 36% (748) for the spine and 33% (675) for the hip of our normal population are classified as osteopenic or osteoporotic. Using MYN values increases the proportion of women classified as osteopenic or osteoporotic to 52% (1078) for the spine and 68% (1409) for the femur. If both sites of measurement are considered simultaneously SYN classifies 46% (952) as either osteopenic or osteoporotic at one or other site, which is increased to 73% (1513) when the MYN values are used. We observe that manufacturer's reference ranges may not be appropriate for the local population and may lead to an erroneously high diagnosis of osteopenia and osteoporosis, which would lead to unnecessary patient anxiety and perhaps errors regarding treatment.     

Variation in bone mineral density between different anatomical sites in a normal local population

Bone mineral density (BMD) measured using dual energy X-ray absorptiometry (DXA) can be expressed in terms of standard deviations, above or below mean young adult T-scores and above or below age-matched Z-scores. The differences between the left neck of the femur (LN), right neck of the femur (RN) and lumbar spine (L2-L4) were statistically significant, irrespective of whether expressed as T-scores or Z-scores. Therefore skeletal status assessment should involve as many sites as practically possible. Considering the low radiation dose and short scanning time, it is suggested that at least the two femurs and lumbar spine BMD be used in routine osteoporosis risk assessment.     

Prevalence of reduced bone mineral density in systemic lupus erythematosus and the role of steroids

OBJECTIVE: To determine the prevalence of reduced bone mineral density (BMD) in a large female cohort of systemic lupus erythematosus (SLE) and to determine the role of steroids and disease related variables. METHODS: All females with SLE managed by rheumatologists affiliated with a single center were invited to undergo BMD measurement of the lumbar spine and left femoral neck by dual energy X-ray absorptiometry (DEXA), standardized examination, and medical record review. RESULTS: Ninety-seven females with a mean (SD) age of 44.2 (14.9) years were studied. Low bone mass [defined as BMD > 1 standard deviation (SD) below young adult mean] was present in 44.3 and 42.1% at the lumbar spine and femoral neck, respectively. Osteoporosis (defined as BMD > 2.5 SD below young adult mean) was present in 13.4 and 6.3% at the lumbar spine and femoral neck, respectively. Steroid usage showed a strong inverse relationship with BMD in the lumbar spine, but a less strong relationship in the femoral neck. CONCLUSION: The findings of high prevalence of reduced BMD and association with steroid therapy have important implications for the routine management of SLE.     

Intracellular hyperthermia for cancer using magnetite cationic liposomes: an in vivo study

OBJECTIVE: Only two previous studies have assessed the effects of long-term GH replacement therapy on bone mineral density (BMD) in patients with adult onset GH deficiency. To date no study has looked at the long-term impact on BMD after a short course (6-12 months) of GH replacement. In two groups of patients with adult onset GH deficiency we have studied BMD either (a) after 3 years of continuous GH replacement or (b) 2 years after completion of a short course of GH. DESIGN: An open GH therapeutic study in which patients were recruited from a previous double-blind placebo-controlled study. The BMD status of all patients was unknown to the physician and patient at the time of recruitment. PATIENTS: Group A (n = 7, three females) all received GH replacement continuously for 3 years. Group B (n = 8, five females) included six patients who received GH replacement for 6 months and two who received GH replacement for 12 months with BMD being measured at 6-monthly intervals. METHODS: Single photon absorptiometry (SPA) and later single X-ray absorptiometry (SXA) were used to measure forearm cortical BMD. Dual-energy X-ray absorptiometry (DXA) was used to measure lumbar spine, trochanteric, femoral neck and Ward's area BMD. RESULTS: In group A lumbar spine and trochanter BMD had increased significantly from baseline by 3.7% (DXA: median change = 0.045 g/cm2; P = 0.028) and 4.0% (DXA: median change = 0.031 g/cm2; P = 0.046), respectively. There were non-significant decreases in femoral neck (1.9%) (DXA: median change = -0.02 g/cm2; P = 0.39), Ward's area (6.5%) (DXA: median change = -0.06 g/cm2; P = 0.09) and forearm (2.6%) (SPA/SXA: median change = -0.013 g/cm2; P = 0.18). In group B, compared with baseline, only trochanter BMD changed significantly, increasing by 5.9% (DXA: median change = 0.0485 g/cm2; P = 0.049). Lumbar spine (DXA: median change = -0.001 g/cm2) Ward's area (DXA: median change = 0.0135 g/cm2), femoral neck (DXA: median change = -0.005 g/cm2) and forearm cortical (SPA/SXA; median change = -0.01 g/cm2) BMD did not change significantly (P = 0.67, P = 0.57, P = 0.86 and P = 0.31, respectively). Median percentage changes compared with baseline were -0.1%, 1.8%, -0.5% and -2.1%, respectively. From the time of completion of GH therapy however, BMD increased significantly at lumbar spine, (median change = 0.023 g/cm2), Ward's area (median change = 0.03 g/cm2) and trochanter (median change = 0.056 g/cm2) (P = 0.036, P = 0.049 and P = 0.012, respectively) but not at the femoral neck (median change = 0.017 g/cm2; P = 0.31) or forearm (median change = 0 g/cm2; P = 0.75). CONCLUSION: Long-term GH replacement therapy for three years appears to have beneficial effects on bone in patients with adult onset GH deficiency particularly at the lumbar spine and trochanter; the effects on femoral neck and forearm cortical BMD, however, are less impressive. A short course (6-12 months) of GH replacement therapy results in an increase in trochanter BMD several years later, and after an initial decline in BMD whilst on GH replacement, lumbar spine and Ward's area BMD return towards their baseline values. These results emphasize that not all types of bone and skeletal sites respond to GH therapy identically. Furthermore a short course of GH replacement over 6-12 months may result in significant changes in BMD several years later.     

Femoral and spinal bone mineral density in Japanese osteoporotics with hip fracture

In the present study, bone mineral density (BMD) of femoral neck and lumbar spine was compared between 38 Japanese female patients with hip fracture (age 63-89 years, mean +/- SD 76 +/- 7 years) and 162 age-matched female controls (age 62-90 years, mean +/- SD 75 +/- 7 years). BMD was measured in the femoral neck and lumbar spine (L2-4) using dual-photon absorptiometry (Norland model 2600). BMD values of femoral neck as well as lumbar spine were significantly lower in patients with hip fracture than in controls (0.504 +/- 0.097 v 0.597 +/- 0.101, p < 0.01, for femoral neck; 0.661 +/- 0.146 v 0.720 +/- 0.128, p < 0.05, for lumbar spine). Patients with hip fracture and controls were stratified according to their BMD levels at two measuring sites, and the ratio of the number of patients and controls at each BMD level was calculated as an indicator of fracture rate. This ratio showed an exponential increase as the femoral neck BMD declined, but only a gradual increase as the lumbar spine BMD declined. Specificity-sensitivity analysis revealed that BMD values of 0.59 and 0.54 g/cm2 at the femoral neck provided a specificity of 52% and 68% with a sensitivity of 90% and 75%, respectively. These findings suggest that Japanese patients with hip fracture are more osteoporotic than age-matched controls and that the selective measurement of femoral neck would be useful for predicting the risk of hip fracture.     

Insulin-dependent diabetes and psychiatric pathology: general clinical and epidemiologic review

The objective was to determine the diagnostic sensitivity of spinal and femoral dual x-ray absorptiometry (DXA) and to study whether a combination of both sites may enhance discriminatory capability in regard to the presence of vertebral fractures. Spinal and femoral DXA were obtained in 324 postmenopausal women, of whom 90 had at least one vertebral fracture. Age-adjusted logistic regression analyses, ROC analyses, and sensitivity-specificity statistics were used to assess the discriminatory ability of spinal and femoral bone density (BMD) alone and in combination. The age-adjusted odds ratios per standard deviation decrease in BMD (OR) for spinal and femoral measurements were comparable (Ward's triangle: OR = 1.62; femoral neck: OR = 1.51; total hip: OR = 1.47; spine: OR = 1.34). Combining spinal and femoral bone density measurements did not improve diagnostic sensitivity of DXA considerably as compared to using BMD of a single site and adjusting the "fracture threshold." The conclusion drawn is that spinal and femoral BMD measurements using DXA have a comparable diagnostic sensitivity for vertebral fracture discrimination. Different individuals at risk for osteoporosis may be identified using both methods. The clinical usefulness of a combination of two bone density measurements needs further study in a prospective setting.     

Automated evaluation of hip axis length for predicting hip fracture

The hip axis length has been shown in previous studies to be predictive of hip fracture independent of age and femoral bone density. The first studies of hip axis length were performed by manual measurement of dual x-ray absorptiometry (DXA) scan printouts. In this study, an automated analysis procedure is defined using software tools provided by the DXA manufacturer. Manual and automatic hip axis length measurements in 198 women were highly correlated (r = 0.98). Because of scaling factors of the printout, the automatic measurement was 58% longer than the manual value. Precision of the automatic measurement, based upon triplicate DXA scans of 33 women, was 0.07 cm or 0.68%. To define normative data, the hip axis length was measured from femoral DXA scans of 471 female volunteers aged 40-92 scanned on 14 different Hologic QDR-1000 systems. Mean hip axis length was 10.5 cm, with a standard deviation of 0.62 cm. No significant relationship between hip axis length and age was found (r = 0.07, P = 0.15). Based on previously reported odds ratios corrected for femoral bone density, age, height, and weight, an automatic hip axis length measurement of 11.0 cm is associated with a twofold increase in hip fracture risk compared with a woman with an average hip axis length. A hip axis length value of 11.6 cm increases hip fracture risk by a factor of 4 compared with a woman with a normal hip dimension. We conclude that the hip axis length can be easily incorporated into existing DXA hip analysis software in combination with a bone density measurement.(ABSTRACT TRUNCATED AT 250 WORDS)     

Total body studies in normal British women using dual energy X-ray absorptiometry

We report dual energy X-ray absorptiometry (DXA) studies of total body bone mineral and body composition performed in 111 normal caucasian women (aged 42-61). Conventional DXA scans of the lumbar spine and femoral neck were also obtained and each woman completed a detailed questionnaire. Significant correlations were found between total body BMD and BMD in the lumbar spine (r = 0.76) and femoral neck (r = 0.72). We present reference range data for BMD in the total body and in seven subregions of the skeleton. Multiple linear regressions of total body BMD and BMC on weight, height and age showed that the inclusion of height compared with weight and age alone was not statistically significant. The dependence of total body BMD on weight and age was: total body BMD (g cm-2) = 1.043 + 0.0042 x weight (kg) - 0.0039 x age (years) (R = 0.46, SEE = 0.074 g cm2). Body mass derived from DXA scans correlated well with weight measured on scales (r = 0.996, SEE = 0.77 kg). Body composition measurements agreed closely with % body fat estimated from skinfold measurements (r = 0.93), body fat mass estimated from a predictive equation based on weight, height and age (r = 0.91) and % body fat estimated from a predictive equation based on body mass index (r = 0.76). Study precision gave coefficients of variation of 0.6% for total body BMD and 0.7% for % body fat.     

Bone density, bone turnover, and hormone levels in men over age 75

BACKGROUND: Osteoporosis is a substantial problem in older men, with 25% of all hip fractures occurring in men. The mechanisms of bone loss in older men are unknown, but elevated parathyroid hormone (PTH) and diminished testosterone (T) levels are postulated as contributing factors. METHODS: We measured bone mineral density (BMD), sex hormones, bone turnover markers, and calcium regulating hormones in a group of community-living men over the age of 75. RESULTS: Thirty-five men (mean age 79; range 75-88 years) without disease or medication known to affect bone metabolism participated in the study. Whole body BMD was 1.21+/-.15 g/cm2; lumbar spine BMD (L1-L4) was 1.10+/-.15 g/cm2; femoral neck BMD was .77+/-.14 g/cm2; and trochanteric region was .71+/-.13 g/cm2. The femoral neck and trochanteric region values were more than 1 SD below the mean for adult men (age 25-33 years) in 28/35 and 15/35 men, respectively. Deoxypyridinoline levels were above the normal range for premenopausal women in 23% of the men; N-telopeptide and C-telopeptide demonstrated a wide scatter, but the values remained in the normal range. T levels were found to be below normal range for adult men in 12 of 32 (38%) subjects and the PTH levels above the normal range in 8 of 35 (23%) subjects. Bone resorption markers correlated inversely with BMD of the whole body, femur, and spine (r=-.22 to -.48). There was an inverse correlation between total T and spine BMD which became insignificant after correcting for body mass index (BMI). In addition, there was no correlation between free or bioavailable testosterone and BMD. 1,25-(OH)2D levels correlated inversely with BMD at the femur and whole body, but no association was found with PTH or 25 OH-D. CONCLUSIONS: Men over 75 years of age had a wide range of BMD but frequently had low values at femoral sites. T levels were below the normal range in 38% of men, and PTH levels were elevated in 23% of men. There was an inverse correlation between total T and spine BMD which may have been dependent on the common effect of BMI. Bone mineral density was inversely related to markers of bone resorption.     

Osteoporosis in male and female leprosy patients

We measured the bone mineral density (BMD) of 353 leprosy patients (197 males 50-89 years old, average age 70.2; and 156 females 53-90 years old, average age 72.9) and serum levels of free testosterone (FT) in 81 males. The BMD of the lumbar vertebrae (L2-L4), diaphysis of the radius (1/3 radius), and the neck of the femur (neck) was measured using DXA (QDR 4500). The BMD of -2.5 SD YAM (young adult mean) in Japanese men and women was used as the cutoff value for osteoporosis in the respective genders: BMD of L2-L4, 0.751 g/cm2 (male), 0.747 g/cm2 (female); 1/3 radius, 0.655 g/cm2 (male), 0.550 g/cm2 (female); neck, 0.581 g/cm2 (female). The percentages of males with osteoporosis were 31.3% in the 50th, 32.9% in the 60th, 44.9% in the 70th, and 40.7% in the 80th decade at L2-L4. Similarly, the percentages were 33.3%, 58.3%, 74.3%, and 75.0%, respectively, at 1/3 radius. Among females, the percentages were 22.2%, 41.3%, 44.9%, and 68.8%, respectively, at L2-L4; 0%, 42.9%, 89.5%, and 78.6%, respectively, at 1/3 radius; and 11.1%, 38.6%, 67.7%, and 84.6% respectively, at neck. FT in men ranged from almost 0 to normal at each decade and BMD levels were significantly correlated with FT in all three regions of the skeleton (P < 0.0001). More than 30% of osteoporosis was found at each decade and FT may be one of the main factors affecting BMD in male leprosy patients.     

Dual-energy X-ray absorptiometry for histologic bone sections

In fundamental osteoporosis research precise and accurate assessment of the mineral quantity in histological bone sections is of particular importance when studying the local effects of implants releasing bone modulating agents. A potentially useful technique to estimate the bone mineral density (BMD) is dual-energy X-ray absorptiometry (DXA). A highly collimated (0.13 mm) Hologic 2000 with a line spacing and point resolution of 0.13 mm was used. The mineral content was measured in regions of 3.1 mm(2). A ceramic hydroxyapatite (CHA) phantom was developed as a reference standard. The phantom was made of a single-phase hydroxyapatite starting powder by compressing and sintering at 1000 degrees Celsius. The true density was 3.14 + or - 0.001 g/cm(3). The calcium/phosphorus ratio was close to the theoretical one of 1.67. The mean precision error expressed as the coefficient of variation (CV) of the mineral density (MD) measurements of the phantoms with thicknesses of 1, 2, and 3 mm was 0.2%. Embedded undecalcified alveolar bone sections of dogs (0.0015-1 mm in thickness) were scanned simultaneously with a phantom 1 mm in thickness. The precision error (CV) of the BMD measurements calculated by DXA for sections > or = 0.1 mm and with a BMD > or = 0.14 g/cm(2) was 0.81%. There was a linear relationship between the BMD calculated by DXA and the estimated BMD in the histological bone sections by means of the true density of the phantom. It is concluded that DXA using a standard CHA phantom is a precise and accurate method to measure MD changes as small as 1% in histological bone areas of 3.1 mm(2) provided that the loss or gain in BMD is > or = 0.14 g/cm(2).     

Large radiolucent lesion of the maxilla

In this cross-sectional study we investigated the effect of compressive and tensile forces applied on the proximal femur during weight-bearing activities. Ninety-seven men (29.9 +/- 1.7 years) were divided into two groups: 69 exercisers who had practiced regular high-impact weight-bearing activities for at least 5 years and 28 controls who had been sedentary for at least 5 years. The maximum isometric hip abduction strength was measured. The bone mineral density (BMD) of the femoral neck and the greater trochanter was assessed using dual-energy X-ray absorptiometry (DXA). Controls were considered as the reference population to calculate the Z score. Mean BMD values of the femoral neck were 0.97 g/cm2 on both sides in the exercisers and 0.83 g/cm2 on the right side and 0.84 g/cm2 on the left side in the controls. Mean BMD values of the greater trochanter were 0.86 g/cm2 on the right side and 0.87 g/cm2 on the left side in the exercisers, 0.73 g/cm2 on the right side and 0.72 g/cm2 on the left side in the controls. The BMD was significantly higher in exercisers at both trochanteric and cervical sites (P = 0. 0001). Both left and right hip abduction strength was significantly greater in the exercisers than in the controls (P < 0.05) and was positively correlated to cervical and trochanteric BMD (P < 0.01). In the exerciser group, the trochanteric Z score was higher than the cervical Z score at both right (P = 0.06) and left (P = 0.002) sides. Therefore, the proximal femoral BMD was significantly greater in exercised subjects as compared with sedentary controls. The difference was observed at the level of both the femoral neck (where it is known anatomically that only compressive gravitational forces are exerted) and the greater trochanter (where it is known that tensile forces are exerted). This result suggests the participation of both compressive and tensile forces in the mechanisms by which exercise influences bone trophicity.     

Development of mass, density, and estimated mechanical characteristics of bones in Caucasian females

Three hundred and thirty healthy Finnish girls and premenopausal women, aged 7-47 years, were examined to evaluate the natural development of bone mineral mass and density from early childhood to menopause. Bone mineral content (BMC,g) and areal density (BMD, g/cm2) were measured from the spine (L2-L4), femoral neck, trochanter region of the femur, and distal radius using dual-energy X-ray absorptiometry (DXA). In addition, the bone mineral apparent density (BMAD, g/cm3) was assessed from the above described skeletal sites, and the mechanical competence of the femoral neck was estimated. Special attention was paid to the timing of the peak values of these bone parameters as well as to the evidence of premenopausal bone loss. The BMC, BMD, and BMAD of the spine, femoral neck, and trochanter region of the femur achieved peak values around the age of 20, and the bone loss seemed to start soon thereafter. In contrast, the bone mass of the distal radius slightly increased between the ages of 20 and 47. In the femoral neck, the estimated bending strength achieved its peak value around the age of 20 and showed a slight decrease during the following decades. The highest body weight and neck-length adjusted strength values of the femoral neck were, however, found in early childhood, with the values decreasing linearly thereafter. In conclusion, this study supports previous findings of rapid bone mineral accumulation in late adolescence, and occurrence of the peak bone mass and density around the age of 20. Premenopausal bone loss seems to occur in the proximal femur and lumbar spine. Our observations of femur strength development imply that from childhood to menopause the mechanical strength of the femoral neck is well adjusted to the biomechanical loading requirements of the body.     

Hereditary nonpolyposis colorectal cancer (HNPCC): eight novel germline mutations in hMSH2 or hMLH1 genes

The World Health Organization criteria for the diagnosis of Osteopenia and Osteopoposis was applied to a control group of 33 females ages 50 to 59 years and 24 females ages 60 to 69 years. The general exclusion criteria for the selection of subjects included early menopause and diseases, use of drugs and toxic habits such as smoking and alcoholism, known to affect bone and mineral metabolism. Bone mineral densities were measured with a DEXA Hologic, model 1000. In the reference population mean peak bone mineral density expressed in g/cm2 was 1.051 (SD = 0.119) for the lumbar spine at age 30 to 39 years and for the femoral neck 0.861 (SD = 0.098) at age 20 to 29 years. Bone densities below 1 to 2.5 SD from mean peak bone mass ranged from 0.932 to 0.754 g/cm2 in the lumbar spine and 0.763 to 0.616 g/cm2 for the femoral neck. The mean age of the pooled group was 58.4 years. The prevalence of osteopenia in the pooled group was 42 % for the lumbar spine and 56% for the femoral neck and of osteoporosis, 12% for the lumbar spine and 8.7% for the femoral neck. A similar prevalence has been found by other investigators in hispanic populations. Such a high percentage of females with osteopenia implicates that bone densitometry must be done in the perimenopausal years and in young individuals at risk so as to proceed with early medical intervention to prevent osteoporosis.     

The effect of long-term thyroxine on bone mineral density and serum cholesterol

The effect of thyrotrophin suppression on bone mineral density (BMD) and serum cholesterol concentration was assessed in 31 treated hypothyroid women. Measurements of the BMD of the lumbar spine and femoral neck were repeated in seven of those with the lowest value after an average period of 22.7 months. Final cholesterol concentrations were compared with values before thyroxine was started. The dose of thyroxine was based on clinical assessment, serum triiodothyronine concentrations kept within the normal range, and thyrotrophin values within the normal range or suppressed. The patients had taken thyroxine replacement for a mean of 12.7 years. Two-thirds (21 subjects) had suppressed thyrotrophin concentrations, and it was normal in one-third (10). Fifteen subjects had a past history of thyrotoxicosis. BMD and cholesterol concentrations were compared between those with suppressed and normal thyrotrophin concentrations and between those with and without a past history of thyrotoxicosis. No patient had a pathological fracture. One had a Z value for the femoral neck of -1.6, denoting early but definite osteoporosis, and five had borderline osteoporosis with Z values for one or other site between -1.1 and -1.5. None of the seven with the lowest BMDs had any significant change when measurements were repeated. The difference in Z values between subjects with suppressed and normal thyrotrophin concentrations was not significant for either the lumbar spine (p = 0.68) or the femoral neck (p = 0.28). A past history of thyrotoxicosis had a greater effect on BMD for both sites than thyrotrophin suppression, but again the difference between those with and without a past history of thyrotoxicosis was significant neither for the lumbar spine (p = 0.18) nor for the femoral neck (p = 0.34). The combination of thyrotrophin suppression and a past history of thyrotoxicosis also failed significantly to reduce the BMD of the lumbar spine (p = 0.38) or femoral neck (p = 0.30) in comparison with those who had neither thyrotrophin suppression nor a past history of thyrotoxicosis. The mean fall in serum cholesterol concentration was 2.1 mmol/l (SD 1.78) (p = 0.001) in those with a suppressed thyrotrophin concentration taking a mean daily dose of thyroxine of 171 micrograms (SD: 34.7), compared with a fall of 0.89 mmol/l (SD: 1.04) (p = 0.065) in those whose thyrotrophin concentration was not suppressed on a mean daily thyroxine dose of 140 micrograms (SD: 50). No patient had atrial fibrillation or cardiographic evidence of coronary artery disease (CAD). The serum cholesterol concentration should play at least as important a part in influencing the dose of thyroxine as a fear of osteoporosis. Fractures are not a feature in the natural history of treated hypothyroidism, whereas CAD is a common cause of death in these patients.     

Identification of metabolic bone disease in patients with endogenous hyperthyroidism: role of biological markers of bone turnover

Active hyperthyroidism is associated with reduced bone mass. Nevertheless, not all patients show the same risk for developing osteoporosis. Our aim was to analyze some clinical and biochemical potential predictors of low bone mass in hyperthyroid patients. We studied 127 consecutive hyperthyroid patients (110 females, 17 males; aged 42 +/- 16 years). Bone mineral density (BMD) was measured by dual X-ray absorptiometry (DXA) at lumbar spine (LS; L2-L4) and femoral neck (FN). Data were expressed as g/cm2 and T-score. Patients were placed into two groups based on recent WHO criteria: Group A, no osteoporosis (n = 98); and group B, lumbar or femoral osteoporosis (n = 29). Study protocol included evaluation of osteoporosis risk factors, anthropometrical variables, thyroid function, and bone turnover markers. Receiver-operating characteristic (ROC) plots for the precision of bone markers and multivariate analysis for the prediction of BMD and osteoporosis were performed. Group B showed greater age and proportion of menopausal females; lower weight, height, and calcium intake; longer duration of menopause; and greater levels of total and bone alkaline phosphatase and of urine hydroxyproline. No differences in thyroid function, osteocalcin, tartrate-resistant acid phosphatase, and type I collagen C-telopeptide (ICTP) were found. The best predictive model accounted for 46% and 62% of the variability of lumbar and femoral BMD respectively and correctly classified 89% of the osteoporotic hyperthyroid patients. No significant difference in ROC plots was observed. It is concluded that hyperthyroid patients with lumbar or femoral osteoporosis show a typical clinical and biochemical profile illustrating that the relationship between BMD and bone markers is better in high turnover states. Classical bone turnover markers show high performance in the evaluation of hyperthyroid bone disease.     

Dual-energy X-ray absorptiometry in osteonecrosis of the femoral head

Osteonecrosis of the hip classically produces a heterogeneous density in the femoral head, although the bone marrow ischemia extends down to the femoral neck and trochanters. Also, bone insufficiency fractures due to diffuse bone loss have been implicated in the genesis of osteonecrosis. OBJECTIVES: To use dual-energy X-ray absorptiometry to quantify the bone changes produced by osteonecrosis of the hip and to compare bone mineral density values in patients with osteonecrosis of the hip and in controls. METHODS: Bone mineral density was measured at the femoral neck (total femoral neck, Ward's triangle, and trochanter), femoral head and lumbar spine using dual-energy X-ray absorptiometry (DPX, L Lunar) in 22 patients with osteonecrosis of the hip and in 22 age- and sex-matched controls. RESULTS: In the patients with osteonecrosis, bone mineral density on the affected side was higher than on the opposite side at the femoral head (+18%), femoral neck (+7%), and Ward's triangle (+6%) and lower at the trochanter (-4%). These differences were most marked at the more advanced end of the osteonecrosis spectrum. As compared to age-specific normative values, the osteonecrosis patients had moderately decreased bone mineral density values at the lumbar spine (-0.53 +/- 1.1 SD or -6 +/- 1.5%) and at the femoral neck on the normal side (-0.9 +/- 1.4 SD or 12 +/- 1.8%). As compared to the controls, bone mineral density was significantly decreased at Ward's triangle (-25%; P: 0.04) and nonsignificantly decreased at the lumbar spine (-4.7%; P: 0.15) and at the femoral neck (-15%; P: 0.09).     

Hip fracture prediction in elderly men and women: validation in the Rotterdam study

The aim of our study was to validate a hip fracture risk function, composed of age and femoral neck bone mineral density (BMD). This estimate of the 1-year cumulative risk was previously developed on the basis of Dutch hip fracture incidence data and BMD in men and women. A cohort of 7046 persons (2778 men) aged 55 years and over was followed for an average of 3.8 years. The 1-year hip fracture risk estimate was calculated for each participant according to the risk function and categorized as low (<0.1%), moderate (0.1 to < 1%), or high (> or =1%). Observed first hip fracture incidence was then analyzed for each of these risk categories by age and gender. Additionally, we calculated the relative risk per standard deviation (SD) decrease in femoral neck BMD in this population. At baseline, 2360 individuals were categorized as low risk, 2567 as moderate risk, and 378 as high risk During follow-up, 110 first hip fractures were observed corresponding to an incidence rate of 4.1/1000 person-years (pyrs) (95% confidence interval 3.4-5.0). The observed incidence rate in the low risk group was 0.2/1000 pyrs (0.1-0.9), 2.7/1000 pyrs (1.8-3.9) in the moderate risk group, and 18.4/1000 pyrs (12.4-27.2) in the high risk group. Below the age of 70 years, incidence was low in all categories, and very few individuals were considered at high risk Above the age of 70 years, the observed incidence was high in the high risk group, while in the low and moderate risk groups, the incidence remained low even over 80 years of age. In women, the age-adjusted relative risk for hip fractures was 2.5 per SD decrease in femoral neck BMD (1.8-3.6), while in men this relative risk was 3.0 per SD (1.7-5.4). In conclusion, we observed a similar relation of hip fracture with femoral neck BMD in men and women and were able to predict accurately hip fracture rates over a period of almost 4 years.