Progression of atypical femur stress fracture after discontinuation of bisphosphonate therapy.

Atypical femur fracture (AFF) is an uncommon complication of long-term bisphosphonate use, but the risk declines substantially after treatment cessation. We report a case of a 70-year-old woman with osteopenia treated with alendronate for 9 years who presented with right mid-thigh pain and radiographic findings of focal lateral cortical thickening in the right mid-femur and lateral cortex irregularity in the proximal-mid left femur. Alendronate was discontinued, but she remained on estrogen for menopausal symptoms. Four years later, a horizontal linear translucent defect was seen in the right mid-femur area of cortical hypertrophy, consistent with an incomplete AFF. The patient underwent prophylactic intramedullary rodding of the right femur and estrogen was discontinued. Three years later (7 years after initial presentation), the cortical irregularities in the left femur were more prominent and three small horizontal linear translucent defects were now evident, consistent with early incomplete atypical fracture development. The patient also suffered a wrist fracture. She was treated with teriparatide for 1.5 years with resolution of the translucent defects in the left but not the right femur, although abnormal thickening of the lateral cortex persisted in both femurs. Our case demonstrates incomplete atypical femur fracture progression in a patient with long-term bisphosphonate exposure, even after treatment cessation. These findings highlight the importance of follow-up for patients who develop diaphyseal femur stress fractures and the potential for early healing with anabolic therapy. This case also demonstrates the challenge in managing older patients with incomplete AFF at risk for progression to complete AFF and osteoporotic fracture.

Atypical femur fracture incidence in women increases with duration of bisphosphonate exposure.

In a northern California population of older women who were treated with oral bisphosphonate drugs, the incidence of atypical femur fracture, a rare complication of treatment, increased with longer duration of bisphosphonate exposure. These findings align with those previously reported in an independent southern California population. INTRODUCTION: The age-adjusted incidence of atypical femur fracture (AFF) reported in southern California increased with bisphosphonate (BP) exposure, ranging up to 113 per 100,000 person-years for 8-10-year exposure. This study examines the incidence of AFF in a northern California population. METHODS: Women age 45-89 years who initiated oral BP during 2002-2014 in Kaiser Permanente Northern California were followed for AFF outcome, defined by a primarily transverse diaphyseal femur fracture through both cortices, with focal periosteal/endosteal hypertrophy, minimal trauma, and minimal/no comminution. Total BP exposure was determined from dispensed prescriptions. The incidence of AFF, calculated for 2-year BP categories ranging from < 2 to > 10 years, was age-adjusted using the 2000 US Census. RESULTS: Among 94,542 women, 107 experienced an AFF during or < 1 year after BP cessation (mean exposure 6.6 ± 3.0 years and total days' supply 5.7 ± 2.8 years at AFF). A strong relationship between AFF incidence and increasing BP exposure was seen, more than doubling for each 2-year category until 8-10 years. Among women with 2- to < 4-year BP, the crude and age-adjusted incidence was 18 and 9 per 100,000 person-years but increased over 2- and 5-fold for women with 4- to < 6- and 6- to < 8-year BP, respectively. For those receiving ≥ 8-year BP, the crude and age-adjusted incidence peaked at 196 and 112 per 100,000 person-years exposure. CONCLUSION: Incidence of AFF increases markedly after 4-6 years of BP. These trends align with southern California and confirm a strong BP duration-related risk of this rare but serious event.

Applying ethnic-specific bone mineral density T-scores to Chinese women in the USA.

Caucasian reference data are used to classify bone mineral density in US women of all races. However, use of Chinese American reference data yields lower osteoporosis prevalence in Chinese women. The reduction in osteoporosis labeling may be relevant for younger Chinese women at low fracture risk. INTRODUCTION: Caucasian reference data are used for osteoporosis classification in US postmenopausal women regardless of race, including Asians who tend to have lower bone mineral density (BMD) than women of white race. This study examines BMD classification by ethnic T-scores for Chinese women. METHODS: Using BMD data in a Northern California healthcare population, Chinese women aged 50-79 years were compared to age-matched white women (1:5 ratio), with femoral neck (FN), total hip (TH), and lumbar spine (LS) T-scores calculated using Caucasian versus Chinese American reference data. RESULTS: Comparing 4039 Chinese and 20,195 white women (44.8 % age 50-59 years, 37.5 % age 60-69 years, 17.7 % age 70-79 years), Chinese women had lower BMD T-scores at the FN, TH, and LS (median T-score 0.29-0.72 units lower across age groups, p < 0.001) using Caucasian reference data. Using Chinese American BMD reference data resulted in an average +0.47, +0.36, and +0.48 units higher FN, TH, and LS T-scores, respectively, reducing the prevalence of osteoporosis (T-score ≤ -2.5) in Chinese women at the FN (16.7 to 6.6 %), TH (9.8 to 3.2 %), and LS (23.2 to 8.9 %); osteoporosis prevalence at any one of three sites fell from 29.6 to 12.6 % (22.4 to 8.1 % for age 50-64 years and 43.2 to 21.0 % for age 65-79 years). CONCLUSION: Use of Chinese American BMD reference data yields higher (ethnic) T-scores by 0.4-0.5 units, with a large proportion of Chinese women reclassified from osteoporosis to osteopenia. The reduction in osteoporosis labeling with ethnic T-scores may be relevant for younger Chinese women at low fracture risk.

Racial/ethnic differences in hip and diaphyseal femur fractures.

UNLABELLED: Contemporary femur fracture rates were examined in northern California women and compared by race/ethnicity. During 2006-2012, hip fracture rates declined, but diaphyseal fracture rates increased, especially in Asians. Women with diaphyseal fracture were younger and more likely to be bisphosphonate-treated. These disparities in femur fracture should be further examined. INTRODUCTION: The epidemiology of diaphyseal femur fracture differs from proximal femur (hip) fracture, although few studies have examined demographic variations in the current era. This study examines contemporary differences in low-energy femur fracture by race/ethnicity in a large, diverse integrated health-care delivery system. METHODS: The incidence of hip and diaphyseal fracture in northern California women aged ≥50 years old during 2006-2012 was examined. Hip (femoral neck and pertrochanteric) fractures were classified by hospital diagnosis codes, while diaphyseal (subtrochanteric and femoral shaft) fractures were further adjudicated based on radiologic findings. Demographic and clinical data were obtained from health plan databases. Fracture incidence was examined over time and by race/ethnicity. RESULTS: There were 10,648 (97.3 %) hip and 300 (2.7 %) diaphyseal fractures among 10,493 women. The age-adjusted incidence of hip fracture fell from 281 to 240 per 100,000 women and was highest for white women. However, diaphyseal fracture rates increased over time, with a significant upward trend in Asians (9 to 27 per 100,000) who also had the highest rate of diaphyseal fracture. Women with diaphyseal fracture were younger than women with hip fracture, more likely to be of Asian race and to have received bisphosphonate drugs. Women with longer bisphosphonate treatment duration were also more likely to have a diaphyseal fracture, especially younger Asian women. CONCLUSION: During 2006 to 2012, hip fracture rates declined, but diaphyseal fracture rates increased, particularly among Asian women. The association of diaphyseal fracture and bisphosphonate therapy should be further investigated with examination of fracture pattern.

Performance of FRAX in a cohort of community-dwelling, ambulatory older men: the Osteoporotic Fractures in Men (MrOS) study.

UNLABELLED: We evaluated performance of FRAX in older men who participated in the Osteoporotic Fractures in Men (MrOS) study. INTRODUCTION: FRAX has been extensively studied in women, but there are few studies of its performance in men. METHODS: FRAX estimates for 10-year hip fracture and major osteoporotic fracture (MOF; either hip, clinical spine, forearm, or shoulder) were calculated from data obtained from MrOS participants and compared to observed 10-year fracture cumulative incidence calculated using product limit estimate methods, accounting for competing mortality risk. RESULTS: Five thousand eight hundred ninety-one men were followed for an average of 8.4 years. Without bone mineral density (BMD) in the FRAX model, the mean 10-year predicted fracture probabilities for hip and MOF were 3.5% and 8.9%, respectively; addition of BMD to the calculations reduced these estimates to 2.3% and 7.6%. Using FRAX without BMD, predicted quintile probabilities closely estimated cumulative incidence of hip fracture (range of observed to predicted ratios 0.9-1.1). However, with BMD in the FRAX calculation, observed to predicted hip fracture probabilities were not close to unity and varied markedly across quintiles of predicted probability. For MOF, FRAX without BMD overestimated observed cumulative incidence (range of observed to predicted ratios 0.7-0.9) and addition of BMD did not improve this discrepancy (range of observed to predicted ratios 0.7-1.1). Addition of BMD to the calculation had mixed effects on the discriminatory performance of FRAX, depending on the analysis tool applied. CONCLUSION: Among this cohort of community-dwelling older men, the FRAX risk calculator without BMD was well calibrated to hip fracture but less well to MOF.

The impact of subtrochanteric fracture criteria on hip fracture classification.

SUMMARY: Hospital diagnosis codes are useful for assessing hip fracture rates in large populations. However, these codes do not reliably differentiate hip fractures that occur in the subtrochanteric region. Identification of subtrochanteric fractures requires review of radiographic images to distinguish these fractures from the more commonly occurring trochanteric fractures. PURPOSE: This study examines the accuracy of coded hospital diagnoses for hip fracture compared to fracture site verification based on operative and radiologic data. The variability in subtrochanteric fracture assignment was also examined using different anatomic criteria. METHODS: This retrospective study includes female members of Kaiser Permanente Northern California age 60 years and older with nontraumatic hip fracture during 2007-2008. Anatomic site was verified by operative and radiologic records, including radiographic image review for fractures occurring in the subtrochanteric region. Two different criteria were compared for subtrochanteric fracture. RESULTS: We identified 2,824 women with incident hip fracture during the 2-year period. The average age was 82.9 ± 8.2 years and 15% were non-White. International Classification of Diseases, Ninth Revision (ICD-9) coding was accurate for femoral neck and trochanteric fractures (>90% confirmed by operative/radiologic reports), compared to only 26% for subtrochanteric fractures using the Orthopedic Trauma Association (OTA) criteria for subtrochanteric fracture. Using OTA classification, 1.3% of hip fractures were assigned as subtrochanteric compared to 4.2% when the criteria were broadened to include the lesser trochanter. Both femoral neck and pertrochanteric fracture rates increased exponentially with age, while age-related rates in subtrochanteric fracture differed by diagnostic classification method; the broader criteria including the lesser trochanter produced age-related trends that mirrored femoral neck and pertrochanteric fractures. CONCLUSION: Unlike femoral neck and pertrochanteric fractures, epidemiologic studies of subtrochanteric fractures cannot rely on ICD-9 codes alone. Review of radiologic images using OTA criteria is required for identification of subtrochanteric fractures occurring below the lesser trochanter.

Updated fracture incidence rates for the US version of FRAX.

UNLABELLED: On the basis of updated fracture and mortality data, we recommend that the base population values used in the US version of FRAX be revised. The impact of suggested changes is likely to be a lowering of 10-year fracture probabilities. INTRODUCTION: Evaluation of results produced by the US version of FRAX indicates that this tool overestimates the likelihood of major osteoporotic fracture. In an attempt to correct this, we updated underlying fracture and mortality rates for the model. METHODS: We used US hospital discharge data from 2006 to calculate annual age- and sex-specific hip fracture rates and age-specific ratios to estimate clinical vertebral fracture rates. To estimate the incidence of any one of four major osteoporotic fractures, we first summed these newly derived hip and vertebral fracture estimates with Olmsted County, MN, wrist and upper humerus fracture rates, and then applied 10-20% discounts for overlap. RESULTS: Compared with rates used in the current FRAX tool, 2006 hip fracture rates are about 16% lower, with greatest reductions observed among those below age 65 years; major osteoporotic fracture rates are about one quarter lower, with similar reductions across all ages. CONCLUSIONS: We recommend revising the US-FRAX by updating current base population values for hip fracture and major osteoporotic fracture. The impact of these revisions on FRAX is likely to be lowering of 10-year fracture probabilities, but more precise estimates of the impact of these changes will be available after these new rates are incorporated into the FRAX tool.

First 20 months' experience with use of metformin for type 2 diabetes in a large health maintenance organization.

OBJECTIVE: To assess adherence to prescribing guidelines, continuation rates, population effects on glycemic control, and occurrence of lactic acidosis during the first 20 months of the availability of metformin in a large health maintenance organization. RESEARCH DESIGN AND METHODS: A retrospective cohort study was performed in the 90,000-member diabetes registry of Kaiser Permanente, northern California. Principal study measures were the proportions of patients started on metformin who met prescribing guidelines (previously on sulfonylureas, HbA1c, obesity, creatinine), the change in HbA1c at 6 months after starting metformin, and hospitalization rates for lactic acidosis. RESULTS: A total of 9,875 patients received metformin during this interval. At least 74% were previously treated with sulfonylureas alone, 81% had baseline HbA1c > or = 8.5%, 71% were obese, and 99% had a serum creatinine < or = 1.5 mg/dl. Among patients on sulfonylureas at baseline, those starting metformin had significantly lower HbA1c levels 6 months later than those not started, after adjustment for age, sex, and the higher baseline levels in those started (adjusted difference: 0.5%, P < 0.0001). Patients starting metformin as initial monotherapy also improved significantly, but patients previously treated with insulin (with or without sulfonyl-ureas) had slightly higher follow-up HbA1c levels than similar patients not starting metformin. Continuation of metformin at 12 months was significantly higher for patients previously treated with sulfonylureas than other groups. One probable case of lactic acidosis was identified during 4,502 person-years on metformin. CONCLUSIONS: Adherence to prescribing guidelines was relatively high during metformin's first 20 months of availability. Glycemic control improved substantially for patients previously treated with sulfonylureas. Lactic acidosis was rare.

Models of spinal trabecular bone loss as determined by quantitative computed tomography.

Noninvasive bone densitometry techniques have significantly improved our understanding of the pattern and magnitude of bone loss over the life span. Quantitative computed tomography (QCT) is capable of selectively measuring highly labile trabecular bone in the central portion of the vertebrae. Trabecular bone mineral density (mg/ml) was determined in 538 healthy women ranging in age from 20 to 80 using GE CT/T scanners at 80 kVp. Various statistical regressions were performed for the entire population to describe the general pattern of bone loss from the spine; a cubic model (r = -0.69, SEE = 26.0 mg/ml) was found to be statistically superior (p less than 0.01) to linear, quadratic, or exponential models. An average bone loss was approximated from these regression analyses with a yearly absolute rate of -2.02 +/- 0.097 mg/ml per year (p less than 0.0001). The average rate of change for premenopausal women was -0.45 mg/ml per year (p less than 0.05), for perimenopausal women was -4.39 mg/ml per year (p less than 0.0001) and for postmenopausal women was -1.99 mg/ml per year (p less than 0.0001). QCT values were also stratified into 5 and 10 year age groups and analyzed separately for pre- and postmenopausal women. The 5 and 10 year interval stratification revealed no identifiable bone density decrements prior to midlife using analysis of variance statistical methods; significant losses of bone mineral density were noted to correspond with the usual time of menopause and to continue into old age. Various two-phase regressions were employed using age and menstrual status to improve the description of age- and menopause-related bone loss.(ABSTRACT TRUNCATED AT 250 WORDS)

Contribution of vertebral deformities to chronic back pain and disability. The Study of Osteoporotic Fractures Research Group.

Among 2992 white women aged 65-70 years recruited from population-based listings, we measured radiographic vertebral dimensions of T5-L4 and calculated ratios of heights: anterior/posterior, mid/posterior, and posterior/posterior of either adjacent vertebra. The degree of deformity for each vertebra was analyzed in terms of the number of standard deviations (SD) that ratio differed from the mean ratio calculated for the same vertebral level in this population. We correlated the severity of each woman's worst vertebral deformity with back pain, back disability in six activities of daily living, and height loss since age 25. Only 39.4% of the cohort had no vertebral deformity; 10.2% had a deformity greater than or equal to 4 SD. Vertebral deformities less than 4 SD below the mean were not associated with increased back pain, disability, or loss of height. In contrast, women whose deformity was greater than or equal to 4 SD had a 1.9 (95% CI, 1.5-2.4) times higher risk of moderate to severe back pain and a 2.6 (95% CI, 1.7-3.9) times higher risk of disability involving the back; they were also 2.5 (95% CI, 2.0-3.2) times more likely to have lost greater than or equal to 4 cm in height. All three types of vertebral deformity (wedge, end plate, and crush) were equally associated with these outcomes. Multiple deformities less than 4 SD did not increase the likelihood of these three outcomes, but multiple deformities greater than or equal to 4 SD tended to be associated with increased back pain, disability, and height loss. This large cross-sectional study suggests that vertebral deformities cause substantial pain, disability, or loss of height only if vertebral height ratios fall 4 SD below the normal mean. Much back pain could not be attributed to vertebral deformities, suggesting other causes.

Low thyrotropin levels are not associated with bone loss in older women: a prospective study.

The relationship between excess thyroid hormone and bone loss is controversial. To determine whether low TSH levels, indicating excessive thyroid hormone, are associated with low bone mass or accelerated bone loss in older women, we performed a prospective cohort study of 458 women over age 65 yr participating in the multicenter Study of Osteoporotic Fractures. Three hundred and twenty-three women were randomly selected from the entire cohort of 9704; an additional 135 randomly selected thyroid hormone users were studied. Medical history, medication use, and calcaneal bone mineral density (BMD) were assessed at the baseline visit. Serum was collected and stored at -190 C. Hip and spine BMD were measured approximately 2 yr later, and follow-up calcaneal and hip BMD measurements were obtained after mean follow-up periods of 5.7 and 3.5 yr, respectively. TSH levels were determined in baseline serum samples using a third generation chemiluminescent assay. After adjustment for age, weight, previous hyperthyroidism, and use of estrogen, bone loss over 4-6 yr was similar in women with low, normal, or high TSH. For example, femoral neck bone loss was -0.3%/yr (95% confidence interval, -0.8%, 0.3%) among women with low TSH (< or = 0.1 mU/L) and -0.5%/yr (95% confidence interval, -0.7%, -0.3%) in those with normal TSH (0.1-5.5 mU/L). There were no statistically significant differences in baseline bone mass of the calcaneus, spine, or femoral neck or trochanteric hip subregions. Baseline total hip BMD was 6% lower (P = 0.01) in women with low TSH. Similar results were obtained in analyses confined to women not taking estrogens. We found no consistent evidence that low TSH, a sensitive biochemical marker of excess thyroid hormone, was associated with low BMD or accelerated bone loss in older ambulatory women.

Timing of estrogen replacement therapy for optimal osteoporosis prevention.

To determine whether estrogen initiated at age 60 yr or later reduces rates of bone loss and fracture incidence, we performed a prospective cohort study of 6910 nonosteoporotic women, 65 yr of age or older. Estrogen use, medical history, lifestyle, and anthropometric data were obtained by questionnaire, interview and examination. We identified five patterns of estrogen use: never users (67%); past early users (started under age 60 yr with no current use; 23%); past late users (started at age 60 or later with no current use; 2%); current early users (started under age 60 yr with use both at baseline and 6 yr later; 6.7%); and current late users (started at age 60 or later with use at baseline and 6 yr later; 1.5%). Bone mineral density was measured at the total hip twice, an average of 3.5 yr apart, and at the calcaneus, an average of 5.7 yr apart. Incident nonspine fractures were validated by radiographic report. Bone mineral density was significantly higher among current users, compared with never and past users. The annual rate of hip bone loss was significantly lower in current early users (-0.22%/yr) and current late users (-0.35%/yr) in comparison with never users (-0.6%/yr), past early users (-0.6%/yr), and past late users (-0.72%/yr). During an average of 11.0 yr of follow-up, 1953 nonspine fractures were confirmed. The multiple-adjusted relative risk of nonspine fracture was 0.63 (95% confidence interval 0.51-0.78) among current early users and 0.75 (0.50-1.12) among current late users, compared with never users. Early initiation and long-term continuation of estrogen is associated with a reduction in the risk of nonspine fractures, and initiation at or after age 60 yr with long-term continuation may also be associated with a reduced fracture risk.

Associations between low levels of serum estradiol, bone density, and fractures among elderly women: the study of osteoporotic fractures.

To evaluate the skeletal effects of endogenous serum estradiol, we measured bone mineral density (BMD) at the calcaneus and radius (single photon absorptiometry) and at the hip and spine (dual x-ray absorptiometry) in 274 women aged 65 yr or more who participated in the Study of Osteoporotic Fractures. Lateral radiographs of the thoracic and lumbar spine were also taken, and serum was assayed for estradiol. Those who had estradiol levels from 10-25 pg/mL had 4.9%, 9.6%, 7.3%, and 6.8% greater BMD at total hip, calcaneus, proximal radius, and spine than those with levels below 5 pg/mL. After multiple adjustments, BMD differences remained statistically significant and corresponded to about 0.4 SD. Vertebral deformities were less prevalent among women whose estradiol level exceeded 5 pg/mL; the multiple adjusted odds ratio was 0.4 (95% confidence interval, 0.2-0.8). We conclude that physiologically low estradiol has a salutary effect on the skeleton in elderly women, possibly by reducing skeletal remodeling.

Racial differences in bone density between young adult black and white subjects persist after adjustment for anthropometric, lifestyle, and biochemical differences.

This study tested whether racial differences in bone density can be explained by differences in bone metabolism and lifestyle. A cohort of 402 black and white men and women, ages 25-36 yr, was studied at the Kaiser Permanente Medical Care Program in Northern California, a prepaid health plan. Body composition (fat, lean, and bone mineral density) was measured using a Hologic-2000 dual-energy x-ray densitometer. Muscle strength, blood and urine chemistry values related to calcium metabolism, bone turnover, growth factors, and level of sex and adrenal hormones were also measured. Medical history, physical activity, and lifestyle were assessed. Statistical analyses using t- and chi-square tests and multiple regression were done to determine whether racial difference in bone density remained after adjustment for covariates. Bone density at all skeletal sites was statistically significantly greater in black than in white subjects; on average, adjustment for covariates reduced the percentage density differences by 42% for men and 34% for women. Adjusted bone density at various skeletal sites was 4.5-16.1% higher for black than for white men and was 1.2-7.3% higher for black than for white women. We concluded that racial differences in bone mineral density are not accounted for by clinical or biochemical variables measured in early adulthood.

Bone mass and subtle abnormalities in ovulatory function in healthy women.

Women with occasional anovulatory or short luteal phase menstrual cycles have been reported to lose bone mineral density (BMD) at a greatly accelerated rate compared to women without such abnormalities. To investigate this association, we performed a longitudinal study of BMD in a group of healthy premenopausal women enrolled in a comprehensive study of ovulatory function. Subjects had collected daily urine samples that were analyzed for estrone and progesterone metabolites by enzyme-linked immunoassay. The 53 participants collected urine for an average of 4.1 cycles. Computer algorithms identified 7 (13.2%) women with luteal phase abnormalities (> 1 anovulatory cycle or cycle with luteal phase length < or = 10 days) and 17 (32.1%) women with other menstrual abnormalities. Areal BMD (grams per cm2) was measured at the lumbar spine, hip, and whole body using dual energy x-ray absorptiometry; BMD was measured 2-3 times over an average observation period of 17.5 months. At baseline, women with luteal abnormalities had mean BMD similar to those of the 29 women with no abnormal cycles: lumbar spine, 1.06 vs. 1.09 g/cm2; total hip, 0.95 vs. 0.94 g/cm2; whole body, 1.15 vs. 1.11 g/cm2 (P > 0.10; adjusted for age and weight at baseline, parity, physical activity level, and calcium intake). When compared at follow-up to women with no abnormal cycles, women with luteal abnormalities tended to gain BMD at the spine and hip (P > 0.10). On whole body measurement, women with luteal abnormalities tended to lose BMD compared to women with no abnormal cycles (-1.1%/yr vs. 0%/yr; P = 0.08); however, the magnitude of loss was not unusual for women in this age range and was within the coefficient of variation for replicate measurements. Neither mean luteal phase length, percent time in luteal phase, nor average daily excretion of progesterone metabolites was associated with baseline BMD or percent annual change in BMD at any measurement site. Thus, we did not confirm a relationship between luteal abnormalities and accelerated bone loss in this population of healthy premenopausal women.

Neuropsychiatric function and dehydroepiandrosterone sulfate in elderly women: a prospective study.

BACKGROUND: Though among the most abundant human steroid hormones, the physiologic role of dehydroepiandrosterone and its sulfate (DHEAS) is not known. Our goal was to determine if DHEAS is associated with cognition and mood in older women, and if baseline DHEAS levels are predictive of cognitive decline. METHODS: In a prospective cohort, we studied 394 randomly selected community-dwelling women, aged 65 years or older, currently enrolled in the Study of Osteoporotic Fractures. Subjects were administered a modified Mini-Mental State Exam, Trials B, Digit Symbol, and the Geriatric Depression Scale-Shortened (GDSS), at study onset and 4-6 years later. Serum was obtained at study initiation for DHEAS analysis. RESULTS: DHEAS levels declined with age, as expected. There was no consistent association of DHEAS quartile or log DHEAS with any of the four outcomes, even after multivariate adjustment. Change in cognitive performance overtime was not associated with DHEAS levels. Analysis of the 32 women without any detectable DHEAS compared to those with detectable levels revealed higher measures on the GDSS (mean score 3.4 +/- 3.6 compared with 1.6 +/- 2.3, p = .028) and a higher percentage with depression (21.7% compared with 4.6%, p = .001). CONCLUSIONS: Serum DHEAS is not a sensitive predictor of cognitive performance or decline on a selected neuropsychological battery in elderly community women; however, nondetectable levels may be associated with depression.

Quantitative computed tomography for prediction of vertebral fracture risk.

Vertebral trabecular mineral content and peripheral cortical bone mineral were measured in 94 female and 44 male osteoporotic patients and compared to vertebral mineral values obtained for 323 control subjects in a cross-sectional study. The rate of change of spinal trabecular mineral with age (measured by quantitative computed tomography) in control females averaged 1.2% per year from age 20 to 80, with an accelerated loss demonstrated at the menopause. Trabecular bone mass in male controls declined an average 0.72% per year. Female osteoporotics had a mean decrement of 48 mg cm-3 (39%) compared to age-matched controls, whereas males were decreased 66 mg cm-3 (50%). Radial cortical bone was correlated with spinal mineral in osteoporotics for both males (r = 0.48) and females (r = 0.62). Vertebral compression fractures or wedging was generally absent in patients with vertebral mineral values above 110 mg cm-3, whereas almost all patients with values below 65 mg cm-3 had fractures. Quantitative computed tomography for measurement of vertebral trabecular bone mineral density is useful for defining those patients in whom the risk of vertebral fracture is increased.

Recurrent nephrolithiasis: natural history and effect of phosphate therapy. A double-blind controlled study.

In a double-blind controlled clinical study, 71 patients with recurrent calcium oxalate stones were divided into three treatment groups: those who received potassium acid phosphate, those who received an inert placebo, and those who received a low calcium diet only. Follow-up periods averaged 2.9 years. Although the mean urinary calcium level of the patients who received phosphate was reduced 33 per cent, their renal stone disease did not diminish. Mean urinary phosphorus increased 88 per cent with phosphate treatment but did not correlate with the decrease in urinary calcium, or with treatment success. The data did not suggest that phosphorus and its metabolites retard calcium oxalate crystallization in urine. No evidence appeared for an association of hypercalciuria with severe stone disease, or with a specific clinical or chemical response to phosphate therapy. Patients whose urinary calcium level fell more than 25 percent when dietary calcium was reduced may have excessive gastrointestinal calcium absorption, which appears to be associated with improved chemical response to phosphate therapy.

Recurrence of nephrolithiasis. A six-year prospective study.

Retrospective studies of nephrolithiasis tend to overestimate the severity of the disease and mistakenly ascribe benefits to treatment regimens. The results of a three-year study of recurrent nephrolithiasis in three patient groups adhering to a calcium-restricted diet who were treated with phosphate therapy, placebo or diet alone are re-examined at the close of an additional three-year follow-up period. Nearly half the subjects in all groups remained free of stone for the six-year period. A reduction in the need for lithotomies occurred in all groups. The absence of renal calcification at entry into the study as well as increasing age were associated with a marked reduction in stone passage. Drug therapy should probably be avoided in older patients as well as in those who are free of renal calcifications.

Thyroid functions and serum lipids in older women: a population-based study.

PURPOSE: To determine if thyroid hormone deficiency, manifested by elevated serum thyrotropin (TSH), is associated with alterations in serum lipids in an unselected population of older women. SUBJECTS AND METHODS: Population-based sampling of 279 ambulatory white women over age 65 studied at four US clinical centers, randomly selected from a cohort of 9,704 participants enrolled in the Study of Osteoporotic Fractures. A third-generation chemiluminescent TSH assay and serum lipid levels--total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides--were measured on fasting sera collected at the baseline visit. The cross-sectional relationships between TSH and lipid levels were analyzed. RESULTS: TSH was high (>5.5 mU/L) in 19 women (6.8%), and was low (< or =0.1 mU/L) in 10 (3.6%). After multiple adjustment, LDL-C was 17 mg/dL or 13% higher (95% confidence interval [CI] 1%, 25%), and HDL-C was 6.5 mg/dL or 12% lower (CI -0.2%, -25%) in women with high TSH compared with those with normal TSH. The ratio of LDL-C to HDL-C was 29% greater (CI 4%, 53%) among women with elevated TSH. Although total cholesterol was 8% higher among women with high TSH, this difference was not statistically significant (CI -1%, 15%). High TSH was found in 12% of the women with the combination of high cholesterol (>240 mg/dL), high LDL-C (>160 mg/dL), and low HDL-C (<45 mg/dL); likelihood ratio = 1.8) whereas high TSH was found in only 2.2% of women with normal lipids (likelihood ratio = 0.3). CONCLUSION: Among older white women, high TSH is associated with deleterious changes in serum lipids, particularly HDL-C, LDL-C, and the ratio of LDL-C to HDL-C cholesterol. Women with multiple lipid abnormalities are twice as likely to have an increased TSH.