Fluoride pharmacokinetics and changes in lumbar spine and hip bone mineral density

Debate about the use of fluoride for the treatment of vertebral osteoporosis has centered not only on whether fluoride treatment decreases vertebral fractures, but also the interindividual vertebral bone mineral density (BMD) response, the potential for nonvertebral fractures, as well as side effects and tolerability. These effects may be dose dependent and, in this study, we examine the pharmacokinetics of sodium monofluorophosphate (MFP) in osteoporotic patients and relate this to changes in BMD. Plasma fluoride absorption curves were measured from 0 to 6 h after ingestion of MFP at baseline and during long-term dosing in 21 patients with vertebral osteoporosis (T scores < or = 2). BMD was measured at baseline and at 12 months at the lumbar spine (LS), femoral neck (FN), trochanter, and Ward's triangle. We found that fluoride elimination was inversely related to creatinine clearance. LS BMD increased from a median of 0.77 g/cm2 (range 0.69 to 0.99) at baseline to 0.88 g/cm2 (0.75 to 1.13) (p < 0.001) after 12 months. This equates to a median increase of 12% (range -1.2 to 37). Median femoral neck BMD decreased from 0.75 g/cm2 (0.62 to 0.94) at baseline to 0.69 g/cm2 (0.62 to 0.92) (p = 0.13) after 12 months. This equates to a decrease of -2% (-19 to 10). BMD at the other hip sites also decreased slightly. Changes in LS and FN BMD were not significantly related (r = 0.28, p = 0.29). The various pharmacokinetic parameters measured were not related to changes in LS BMD; however, there was an inverse relationship between trough fluoride concentration during long-term dosing and change in FN BMD. Further studies are required to see if this relationship can be used to monitor osteoporotic patients treated with fluoride and prevent significant decreases in FN BMD and possibly fractures at this site.     

The effect of pamidronate on lumbar spine bone density and pain in osteoporosis secondary to systemic mastocytosis

Orthotopic liver transplantation (OLT) in patients infected with hepatitis B virus (HBV) is known to be associated with a high recurrence rate and poor prognosis. Interferon treatment in these patients offers little benefit and may lead to further complications. Lamivudine, the (-)enantiomer of 3'-thiacytidine, a 2'3'-dideoxynucleoside, is known to be a potent inhibitor of HBV replication in patients with chronic HBV infection. Three HBV-positive OLT patients were administrated lamivudine, 100 mg x 1 orally, for a period of at least 20 weeks, in an open, compassionate-use basis. All three patients were HBV DNA-negative before OLT. HBV reinfection occurred at a median time of 7 months (range, 6-9 months) after OLT, in spite of adequate immunoprophylaxis. All three patients had high serum transaminase levels (alanine aminotransferase [ALT], 103-324 U/L) and histologic evidence of recurrent HBV infection of the grafted liver, and HBV DNA was evident in the sera of all of them. Six weeks after lamivudine treatment, HBV DNA disappeared from the serum of all patients (detected by hybridization); by the 10th week, HBV DNA was also negative by polymerase chain reaction in two out of three patients. Interestingly, the one patient who was HBV DNA positive by polymerase chain reaction still has mildly elevated ALT levels, whereas the other two patients have normal ALT levels. We also noted that on the 5th week there was a transient elevation of serum ALT levels in two patients. No adverse effects or rejection episodes were noted. In conclusion, lamivudine is a beneficial and well-tolerated therapy in OLT patients with recurrent HBV infection. We are studying the effect of lamivudine in other patients and for a longer period of time.     

Peripheral body fat has a protective role on bone mineral density in elderly women

OBJECTIVES: To determine whether bone mineral density is lower in women living in homes for the elderly as compared to free dwelling control subjects, and to investigate factors affecting possible differences. This is the first study with this objective as the primary aim. DESIGN: Case-control study. SUBJECTS AND METHODS: Institutionalised independent elderly women (n = 22, mean age = 75.1 y+/-6.43 s.d.) randomly selected in a home for the elderly and 22 age-matched control women randomly selected from a sample representative of the independent non institutionalised local population who underwent dual energy X-ray absorptiometry (DXA) at the lumbar spine and right femoral neck; anthropometric measurements (height, weight, subscapular and triceps skinfold thickness); general questionnaire. RESULTS: Mean bone mineral density at the femoral neck was 0.618 g/cm2 (+/-0.130s.d.) in institutionalised women and 0.709 g/cm2 (+/-0.106 s.d.) in controls (P = 0.02, t-test). Controlling for confounding factors in the analysis of covariance, triceps skinfold thickness and living in a home for the elderly turned out to be significant determinants of bone mineral density. CONCLUSION: When compared to free dwelling control subjects, institutionalised women show lower bone density, that is the main risk factor for fracture. Reduced peripheral body fat was significantly associated with the low bone mineral density observed. Health programs aimed at decreasing the incidence of fractures among institutionalised subjects will also have to consider the effect of nutritional or life style factors that reduce peripheral body fat.     

Nutrition and bone mineral density in premenopausal women

Environmental factors have an important role in osteoporosis. Diet and, in particular, nutrients like calcium, vitamin D or phosphorus were extensively studied as determinants of bone mineral density, but the results remain conflicting and there is no clear evidence for an independent effect of such factors in the bone density of premenopausal women. We studied 66 healthy premenopausal women (20-40 years-old) aiming to relate bone mineral density, as measured in three different sites (distal forearm, lumbar spine and femoral neck) using single X ray and dual energy X-ray absorptiometry, with nutritional intake as estimated by a semi-quantitative food frequency questionnaire. Demographic, anthropometric and other life style variables were also assessed. There was a significant correlation between distal forearm and femoral neck (r = 0.57) or lumbar spine (r = 0.45) bone mineral density. No significant effect of age was observed for distal forearm bone mineral density in these women. In a stepwise multiple linear regression model, evaluating the contribution of all the variables studied, only body mass index (p=0.038) and vitamin A ingestion (p = 0.020) had an independent contribution for the variation in distal forearm bone mineral density. Mean bone mineral density, assessed in the femoral neck (p = 0.003) or the lumbar spine (p = 0.056) was different across tertiles of alcohol ingestion, being higher in non-drinkers. However, among regular drinkers there was a significant positive correlation between alcohol ingestion and femoral neck bone mineral density (Spearman's r = 0.53, p = 0.015). This study shows that the effect of nutrition seems dependent on the anatomical site assessed and that there is a weak correlation between nutritional intake and the actual bone mineral density.     

Effects of weight and body mass index on bone mineral density in men and women: the Framingham study

We evaluated the association of weight and bone mass in elderly male and female subjects of the Framingham osteoporosis study, a subset of the Framingham study cohort. By examining the differences in the correlations of weight with bone mass among men and women in weight-bearing and non-weight-bearing sites and weight change since early adulthood, we attempted to understand different ways in which weight or body mass index affects bone mass. During biennial examination 20 of the Framingham cohort (1988-1989), 693 women and 439 men (mean age 76 years) had proximal femur bone mineral density assessed by dualphoton absorptiometry (DPA) and radius bone mass assessed by single-photon absorptiometry. The majority of these subjects also had spine measurements by DPA. Subjects had been weighed repeatedly over 40 years. After adjusting for other factors affecting bone density, we found that both recent weight and body mass index explained a substantial proportion of the variance in bone mineral density for all sites in women (8.9-19.8% of total variance, all p < 0.01) and for only weight-bearing sites (femur and spine) in men (2.8-6.9% of total variance, all p < 0.01). For bone mineral density at the proximal radius, weight and body mass index accounted for < 1% of variance in men (p NS). Weight change since biennial examination 1 (1948-1951) was the strongest explanatory factor for bone mineral density among women at all sites, but weight change did not affect radius bone mineral density in men. The effect of weight and of weight change on bone mineral density was in general much less in men than in women. Our results suggest that the strong effect of weight on bone mineral density is due to load on weight-bearing bones sexes. The sex difference is unexplained but may be due to adipose tissue production of estrogen in women after menopause.     

Relationship between spine bone mineral density and vertebral body heights

The aim of this study was to investigate the correlation between lumbar spine bone mineral density (LS-BMD) and the vertebral body heights with advancing age and years since menopause. One hundred and sixty-three women ages 39-74 years (77 normal premenopausal, ages 39-54, and 86 normal postmenopausal, ages 46-74 years) were studied. LS-BMD was measured by dual energy X-ray absorptiometry. Vertebral heights were evaluated, using morphometry, as the sum of anterior (AHs), middle (MHs), and posterior (PHs) vertebral body heights from T4 to L5. The AHs/PHs ratio at the same level was also calculated. AHs, MHs, PHs, and AHs/PHs ratio directly correlated with LS-BMD; the correlations are AHs r = 0.80, P < 0.0001, MHs r = 0.75, P < 0.0001, PHs r = 0.76, P < 0.0001, and AHs/PHs r = 0.66, P < 0.001. Both LS-BMD and AHs are inversely correlated with age, and the regressions fit with both linear and cubic curves. The statistical significance of the correlations persists while maintaining age constant. The linear regression curve of AHs with age indicates that the spine height decrement rate is 2.12 mm/year, corresponding to 7.4 cm in 35 years. AHs decreases immediately after menopause fitting with a cubic curve model, with a decrement rate of about 3 cm in the first 5 years after menopause. We conclude that the measurement of the sum of vertebral body heights could usefully integrate LS-BMD evaluation in the clinical and epidemiological investigation of osteoporosis.     

Pattern of fall and bone mineral density measurement in hip fractures

The objectives of this study were to determine the pattern of fall and the bone mineral density distribution in hip fracture patients. The study was carried out on 260 patients (204 females and 56 males) with hip fractures over a period of three years (i.e. 1991 to 1993). The patients were all above 50 years old and the average age was 77.7 years for women and 76.8 years for men. Information relating to their falls and subsequent hip fractures were collected. Bone mineral density of the contralateral intact femoral neck was measured using dual energy X-ray absorptiometry (Model XR26, Norland Corporation, USA). Bone mineral density in the patients with hip fracture (mean value 0.55 g/cm2) was significantly lower than the fracture threshold value of 0.64 g/cm2. Falls which would result in direct impact on the hip such as sideways, backwards and straight down formed 95.6% of the cohort. Forty-six (17.7%) of the patients fell from a seated or lying position and their bone mineral density were significantly lower (i.e. 0.45 g/cm2). Two hundred and twenty-three (85.7%) of the patients fell on hard surfaces such as ceramic, marble and concrete. Two hundred and twelve (81.5%) of the falls occurred indoors and 153 (58.8%) while walking. Low bone mineral density and falls are important risk factors in hip fracture in the elderly population. Patients with low bone mineral density can sustain a hip fracture from mild trauma such as falling from a seated or lying position. It is therefore necessary to monitor bone mineral density values as well as to prevent or minimise the risk of falling.     

Relationship between nutrient intake and bone mineral density in an urban community of healthy elderly women

The relationship between nutrient intake and bone mineral density (BMD) in a community of healthy elderly women was investigated. A three-day nutritional survey was carried out. Subjects were divided into two groups using criteria set by the Recommended Dietary Allowances for the Japanese Fifth Revision (1994). Relationship between nutritional intake and BMD was explored. Intake of energy, protein, fats, and vitamins B1 and B2 correlated positively with BMD, as did the intake of eggs, meat, legume and soya products, other vegetables and potatoes, as well as fat and oil. Those with larger average number of food ingested per day had higher average of BMD. In conclusion, the hypothesis: adequate dietary intake protects against BMD loss, agreed with the results. Sufficient nutrient and food intake is associated with BMD increase, and possibly reduced risk of osteoporosis.     

The relationship between osteoarthritis and osteoporosis in the spine

We report on the case of a man, whose psychopathological symptoms markedly varied during different phases of his illness, causing difficulties in applying common diagnostic criteria for schizophrenia. Depending upon each of the predominant symptoms, this resulted in different diagnoses and therapeutic strategies. We also discuss the importance of obsessions and compulsions in differential diagnosis in this case.     

Evaluation of low density spine software for the assessment of bone mineral density in children

Pediatric dual-energy X-ray absorptiometry spine scans often cannot be analyzed with standard software due to a failure to identify the bone edges of low density vertebrae. Low density spine (LDS) software improves bone detection compared with standard software. The objective of this study was to compare bone mineral density (BMD) measurements obtained with the standard and LDS software in 27 healthy nonobese, 32 obese, and 41 chronically ill children, ages 2-18 years. Lumbar spine (L1-L4) BMD, measured by standard analysis, ranged from 0.531-1.244 gm/cm2. Reanalysis with the LDS software resulted in a systematic increase (mean +/- SD) in estimated bone area of 17.0+/-5.0%, an increase in bone mineral content of 6.1+/-6.3%, and a mean decrease in BMD of 8.7+/-1.7% (all p < 0.001). This resulted in a mean decrease in BMD Z score of 0.7+/-0.2. Linear regression models, predicting standard BMD from LDS BMD, were fit for the three subject groups (R2 = 0.993-0.995). Small differences in slopes were detected across groups (p = 0.07); LDS BMD predicted higher standard BMD in obese subjects. In conclusion, LDS analysis resulted in a clinically significant decrease in measured BMD. The association between analysis methods was exceptionally high (R2 > 0.99), indicating that LDS BMD accurately predicts standard BMD. Although LDS BMD in obese subjects predicts higher standard BMD results than in nonobese subjects, the small difference is of questionable clinical significance. LDS software is a useful tool for the assessment of BMD in children.     

Hip motion and moments during gait relate directly to proximal femoral bone mineral density in patients with hip osteoarthritis

The present study examined the loads at the hip joint during gait and the bone mineral density of the proximal femur in 25 patients with end-stage hip osteoarthritis. Dual energy X-ray absorptiometry was used to determine the bone mineral density of the greater trochanter, femoral neck and Ward's triangle of the osteoarthritic group. The bone mineral density was normalized for the patient's age, gender, weight and ethnic origin (Z score). Gait analysis was used to determine the external hip joint moments and motion during walking for the osteoarthritic group and a control group of 21 normal subjects. The gait parameters of the osteoarthritic group which were significantly diminished compared to the normal group (p < 0.001) accounted for as much as 42% (p < 0.001) of the variation in the normalized bone mineral density. Specifically, the dynamic sagittal plane hip motion during gait (maximum flexion minus maximum extension) and peak external rotation and adduction moments were significantly correlated with greater trochanter (R = 0.429-0.648, p = 0.032-0.0001) and Ward's triangle (R = 0.418-0.532, p = 0.038-0.006) normalized bone mineral density while the adduction moment was also significantly correlated with the femoral neck normalized bone mineral density (R = 0.5394, p = 0.005). The normalized bone mineral density of the femoral neck and Ward's triangle was elevated while that of the greater trochanter was decreased as compared to normal reference values. The significant correlation between the hip joint moments during gait and femoral bone mineral density indicate that hip joint loads need to be included when explaining local variation in bone mineral density in hip osteoarthritis.     

Bone mineral density and the results of chiari pelvic osteotomy for osteoarthritis of the hip

We present yotari, a novel neurological mutant mouse whose mutation is transmitted in an autosomal recessive manner. The phenotype of yotari is very similar to that of reeler. yotari mutants are recognizable by their unstable gait and tremor and by their early deaths at around the time of weaning. The cerebella of homozygous yotari are hypoplastic and have no foliation. A molecular and a granular cell layer can be identified, but Purkinje cells are scattered throughout both the granular layer and white matter. The laminar structure of the cerebral cortex and the hippocampal formation are also distorted. To test whether the mutated gene in yotari is the reeler gene, reelin, yotari heterozygotes were mated with reeler homozygotes or heterozygotes. The absence of abnormal offspring indicated that the yotari gene is distinct from reelin. Furthermore, expression of mRNA and protein of reelin was verified by Northern blotting and immunohistochemistry using a CR-50 monoclonal antibody (mAb) which is specific to Reelin, the reelin gene product. Although the mutation of several genes, including cyclin-dependent kinase 5 (Cdk 5), p35 and LIS1, 45 kDa subunits of platelet-activating factor acetylhydrolase (PAF-AH) Ib, in Miller-Dieker lissencephaly syndrome (MDS) has been reported to cause abnormal laminar structure in the brain, no abnormality was found in yotari by Western blotting with antibodies (Ab's) against these molecules. The close similarity of the phenotypes of yotari and reeler and the expression of reelin in yotari may suggest that the gene mutated in yotari encodes a molecule that is on the same signaling pathway as Reelin, the product of reelin. yotari will provide valuable clues to explore the molecular mechanism of neuronal migration and orderly laminar structure formation of the brain.     

Effect of carbamazepine and valproate on bone mineral density

OBJECTIVE: To examine the effect of carbamazepine and valproate monotherapy on bone mineral density in children. METHODS: Axial (second, third, and fourth lumbar vertebrae) and appendicular (distal third of radius) bone mineral density was measured by dual-energy x-ray absorptiometry in 27 healthy children and 26 children with uncomplicated idiopathic epilepsy treated with either carbamazepine (n = 13) or valproate (n = 13) for more than 18 months. Control subjects and patients were similar with respect to age, race (all white), and geographic area, and had no dietary restrictions, neurologic impairment, or physical handicaps. RESULTS: Subjects were seizure-free for more than 6 months on a regimen of carbamazepine or valproate therapy, and had mean serum trough levels of 6.88 +/- 2 micrograms/ml and 72.04 +/- 45.6 micrograms/ml, respectively. Dietary calcium intake was similar in control and treated groups. After correction for gender and age, children treated with valproate had a 14% (p = 0.003) and 10% (p = 0.005) reduction in bone mineral density at the axial and appendicular sites, respectively. The reduction in bone mineral density increased with the duration of valproate therapy. Carbamazepine did not significantly reduce bone mineral density. CONCLUSION: Valproate montherapy, but not carbamazepine therapy, significantly reduces axial and appendicular bone mineral density in children with idiopathic epilepsy and may increase their risk of osteoporotic fractures.     

Effect of vitamin D receptor gene polymorphism and lifestyle on bone mineral density and bone mineral density decrement rate

The effects of genetic and environmental factors on bone mineral density (BMD) were investigated in 108 healthy Japanese women. Of the 108 subjects, BMD (from the second to forth lumbar vertebrae) was measured in 1992 in 103, in 1993 in 100, and in both years in 95 by dual energy X-ray absorptiometry. Vitamin D receptor (VDR) gene polymorphism in intron 8 was used as a genetic marker. Information on menstruation, health status, lifestyle, quantities of nutrient intake and frequencies of food intake was obtained by questionnaire. The frequency of allele B (825bp), whose polymerase chain reaction (PCR) products cannot be cut with BsmI, was 0.259 and the frequency of allele b (650bp), whose PCR products can be cut with BsmI, was 0.741. The subjects in our study obeyed the Hardy-Weinberg law. While the frequency of allele B was 0.448 in European whites as reported by Morrison et al, it was 0.259 in our Japanese subjects, suggesting a racial difference. Z score values (average value 0, standard deviation 1) increased in the order BB, Bb and bb. This result indicates that allele B is associated with the lower BMD in Japanese, as in European whites. The BMD decrement rate increased in the order bb, Bb and BB, indicating that VDR gene polymorphism may be a regulatory factor for losing BMD. Most of lifestyle variables, calcium intake and vitamin D intake were not correlated with BMD, but the food frequency score (which was defined as values weighted in each of three food categories obtained by factor analysis) was significantly correlated with BMD. Multiple regression analysis showed significant influences of years after menopause, the food frequency score and VDR genotype on BMD. VDR genotype and years after menopause influenced the BMD decrement rate significantly in multiple regression analysis. Neither a relationship between BMD and calcium intake nor between BMD and vitamin D intake by VDR genotype was found. These results suggest that the VDR gene is a genetic factor in BMD and the BMD decrement rate in Japanese.     

Effect of age and osteoarthritis on bone mineral in rhesus monkey vertebrae

We have used vertebrae of free-ranging rhesus macaques to study the effect of age and osteoarthritis on bone mineralization and bone density and to relate these findings to weight, sex, parity, and mineral chemistry. Bone mineralization was determined using the density fractionation technique and bone density using dual-photon absorptiometry. Arthritis was determined osteologically. We found a relationship between mineralization, age, and osteophytes, such that mineralization rose with age in nonarthritics and decreased with age in arthritics. This could also be seen when the females were examined separately. In males, only an increase in mineralization with age could be seen. In females mineralization decreases with parity. Also in females, DPA density decreases with age and increases with parity. No relationships with DPA density could be seen using males and females together or males alone. In conclusion, we have shown that normal skeletal aging in rhesus monkeys is accompanied by an increase in mineralization similar to that in other species, but this is not true in the presence of osteoarthritis. In the females parity has an important effect because it seems to build up bone mass even though the bone present may be undermineralized.     

Bone mineral density and bone markers in relation to vitamin D receptor gene polymorphisms in Chinese men and women

Whether vitamin D receptor gene (VDRG) polymorphism can be used as a predictor for bone turnover rate or bone mass remains controversial. Its role within various ethnic populations are also unsettled. We examined VDRG polymorphism using restrictive enzymes Bsm-I, Apa-I, and Taq-I in 155 men aged 22-88 and 113 premenopausal women aged 40-53. The bone mineral density (BMD) of the vertebrae (L2-4), proximal femur, and total body bone mineral content (tb-BMC) (women only), as well as urinary N-terminal crosslinked fragment of type I collagen (NTX), serum osteocalcin, bone isozyme of alkaline phosphatase, and caboxyterminal propeptide of type I procollagen levels were measured. Chinese men and women exhibited a low prevalence for B (absence of Bsm-I restriction site) phenotypes than white and Japanese. Within the tested samples there were 0.4% BB homozygotes, 6.7% Bb heterozygotes, and 93% bb homozygotes. The distributions of Apa-I polymorphism (9.0% AA, 42.5% Aa, and 48.5% aa) also differed from those reported for the white populations. Most of the Chinese men and women were TT homozygous (96.6%). A comparison of actual values and values adjusted for age and weight of tb-BMC and BMD at the lumbar spine, Trochanter, Ward's triangle, and femoral neck showed no significant difference among three subgroups in each of the three sets of polymorphism. Furthermore, the actual values and adjusted values (adjusted for age) of the four bone markers, respectively, showed no significant differences. We conclude that given the very low prevalence of the suspected high risk genotypes (B, A, and t), and the lack of difference among the polymorphic subgroups, VDRG polymorphism may not be an important determinant of the bone turnover rate and bone mass of Chinese men and women.     

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.     

Association between insulin-like growth factor I and bone mineral density in older women and men: the Framingham Heart Study

Few studies of the GH axis and bone have focused specifically on elderly people. The objective of this study was to determine the association between insulin-like growth factor I (IGF-I) and bone mineral density (BMD) in 425 women and 257 men aged 72-94 who participated in the Framingham Osteoporosis Study component of the Framingham Heart Study in 1992-1993. Serum IGF-I level was determined by RIA. BMD at three femoral sites and the lumbar spine was determined by dual x-ray absorptiometry, and at the radius by single-photon absorptiometry. IGF-I level was positively associated with BMD at all five sites (Ward's area, femoral neck, trochanter, radius, and lumbar spine) in women after adjustment for weight loss and other factors (P < or = 0.01) and protein intake in a subset of participants (0.006 < P < 0.07). A threshold effect of higher BMD was evident at each of the 3 femoral sites and the spine (P < 0.03) but not at the radius for women in the highest quintile of IGF-I (> or = 179 g/liter) vs. those in the lowest four quintiles. IGF-I was not significantly associated with BMD in men. These results indicate that higher IGF-I levels are associated with greater BMD in very old women, and suggest that future clinical trials employing GH may have a role in the development of treatments for older women with osteoporosis.     

Regional bone mineral density interrelationships in normal and osteoporotic postmenopausal women

We describe a prospective study in which bone mineral density (BMD) was measured in total body and regions, proximal femur, lumbar spine, and forearm in 84 apparently normal postmenopausal women with normal spinal radiographs and in 47 women with 1-10 wedged or compressed vertebrae. There was a history of peripheral fracture in 35 of the 84 controls and 30 of the 47 osteoporotics (p < 0.02) but there was no association between vertebral fracture and wrist fracture. At all sites and regions, the differences in BMD between the "normal"and "osteoporotic" women was highly significant and all but "ribs" and "arms" remained significant after correction for menopausal age. In the whole set, and in both subgroups, the coefficients of correlation between sites and regions were all highly significant (p < 0.001). Nonetheless, some sites discriminated better between the two groups than others. Standardized odds ratios (OR) for vertebral fracture versus no-fracture were calculated by logistic regression and expressed as the rise in OR for each standard deviation (SD) fall in bone density. This ratio was greatest (3.4) in "pelvis" and weakest (1.7) in "ribs" but all were statistically significant. Geometric mean regression equations were calculated for all the 78 possible pairs of sites and regions in the 84 normal subjects and the deviations of the osteoporotic women from these normal slopes calculated. In most pairs of sites and regions, the vertebral fracture cases were scattered around the normal group's slope but fell lower down on both axes. The bone deficits in the osteoporotics compared with young normal women ranged from -14% in "head" to -40% in Ward's triangle and the T-scores ranged from -1.9 in "ribs" to -3.9 in the forearm. Sensitivity ranged from 17% in "ribs" to 36.2% in Ward's triangle. Specificity varied between 88 and 94% and the percent correctly classified ranged from 62.6% in "ribs" to 72.5% in Ward's triangle. We conclude that primary postmenopausal osteoporosis affects the entire skeleton but that some sites discriminate better between vertebral fracture and nonfracture cases regardless of whether they represent cortical or trabecular bone.     

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.