Hip axis length variation: its correlation with anthropometric measurements in women from three ethnic groups.

UNLABELLED: We compared hip axis length (HAL) in 157 non-Hispanic white women, 292 African-American women, and 210 Mexican-American women. After adjusting for maximal hip girth, there were no residual differences in HAL by ethnicity. Differences in hip fracture risk seen between these groups cannot be explained by ethnic differences in HAL. INTRODUCTION: Hip axis length (HAL) has been reported to be an independent predictor of hip fracture. Significant ethnic differences in HAL have been noted, but no direct comparison has been made between African-American, Mexican-American, and non-Hispanic white women using the same protocol. METHODS: We compared 157 non-Hispanic white women from the Rancho Bernardo Study, 292 women from the Health Assessment Study of African-American Women, and 210 women from the Skeletal Health of Mexican-American Women Project. A standardized questionnaire was used to obtain medical history; height, weight, waist girth, and hip girth were measured; and percentage body fat and HAL were obtained using dual energy X-ray absorptiometry. All HAL comparisons were adjusted for maximum hip girth to control for differences in size magnification by fan-beam absorptiometry. RESULTS: Though there were ethnic differences in the unadjusted HAL measurement, after adjusting for hip circumference, there were no residual differences in HAL with regard to ethnicity: 10.7 cm in Mexican-American women vs. 10.8 in non-Hispanic white women and African-American women (p = 0.61). CONCLUSIONS: There were no ethnic differences in HAL in women from the three ethnic groups. Differences in fracture risk among these groups cannot be explained by ethnic differences in HAL.

Breast cancer and bone mass in older women: is bone density prescreening for mammography useful?

INTRODUCTION: The utility of screening mammography for older women with low bone mineral density (BMD) is controversial. This case-control study compares BMD at multiple sites in women with and without breast cancer to determine if BMD prescreening is useful in selecting women for continued screening mammograms. METHODS: Women diagnosed with breast cancer in the preceding 4 months and age-matched controls (+/-2 years) with a normal mammogram, all aged 65 years and older, were recruited on a 1:2 basis; 237 women participated: 79 women (cases) with breast cancer and 158 controls. BMD at the lumbar spine, hip, radius, and whole body was measured with dual x-ray absorptiometry (DXA). RESULTS: Among women with breast cancer, 17.1% had stage 0, 41.5% stage I, 40.0% stage II, and 1.4% stage III. Women with breast cancer had larger waist circumferences (p=0.002) and waist-hip ratios (p=0.01), and they exercised less (p=0.002) than women of the control group. However, there were no differences between the cases and controls for age, obesity, and reproductive and menopausal history variables, or other covariates (p>0.10). There were no differences in lumbar spine, total hip, femoral neck, midshaft radius, or total body BMD (p>0.10), although the cases had higher BMD at the ultradistal radius than the controls (means: 0.527 vs. 0.516, respectively; p=0.014). There were no differences in breast cancer risk by tertile of BMD or osteoporosis status at the hip or spine. CONCLUSION: There is little difference in BMD between women with and without breast cancer. BMD is not useful as a prescreening predicator of mammography in older women and using it as such would result in cases of breast cancer being missed.

Incidence of Clostridium difficile-associated diarrhea before and after autologous peripheral blood stem cell transplantation for lymphoma and multiple myeloma.

Diarrhea is a major cause of morbidity and discomfort for patients undergoing high-dose chemotherapy and autologous peripheral blood stem cell transplantation (APBSCT). There are multiple causes of diarrhea in patients undergoing transplantation including antineoplastic chemotherapy, antimicrobials and infection, including Clostridium difficile as the most common pathogen involved. The purpose of this study was to determine the incidence of C. difficile-associated diarrhea (CDAD) 1 week before and 30 days after APBSCT, and to identify risk factors for the development of CDAD including diagnosis. Two hundred and forty-two patients underwent APBSCT for multiple myeloma and lymphoma between October 1996 and October 2001 in two teaching hospitals. Diarrhea was reported in 157 (64.9%) subjects. One hundred and thirty-five out of the 157 subjects were tested for the presence of C. difficile toxin A. These subjects constitute the study group. The incidence of CDAD was 15%. Two thirds of the patients who developed CDAD had multiple myeloma and one third had lymphoma; this difference did not attain statistical significance. The use of cephalosporins (P = 0.03) and the use of intravenous vancomycin (P = 0.02) were the only identified risk factors associated with the development of CDAD. Patients treated with paclitaxel as part of the mobilization regimen had a lower incidence of CDAD than patients who received hematopoietic growth factor only (P = 0.01).

Adult hepatitis B vaccination using a novel triple antigen recombinant vaccine.

Present hepatitis B vaccines use multidose prolonged regimens, which even healthcare workers at risk do not always complete. Moreover, when vaccination is completed there remain some who fail to achieve adequate protection. The protection of adults at risk could be improved if there were a more potent vaccine and/or a shorter vaccination regimen available. Vaccine-naive adults were randomized to vaccination with either Engerix-B (SmithKline Biologicals, Rixensart, Belgium) or a novel triple antigen (S, pre-S1, and pre-S2) recombinant vaccine (Hepacare; Medeva Pharma Plc, Speke, UK). The primary efficacy parameter was the degree of seroprotection 6 or 7 months (26 +/- 2 weeks) after beginning vaccination. A total of 304 adults entered the study. Of these, 16 failed to complete the study (9 on Hepacare and 7 on Engerix-B). With the Engerix-B standard (0, 1, 6) regimen, 88% of subjects were protected by month 7, whereas with the triple antigen vaccine a 2-dose regimen (0, 1) provided equivalent protection (91%) within 6 months and a 3-dose (0, 1, 6) regimen was significantly superior (98% seroprotected by 7 months after starting vaccination P <.001). With adults at risk for a suboptimal response (i.e., older adults, the obese, men, and smokers) the triple antigen vaccine produced a greater degree of protection. The vaccines had similar safety profiles. Both vaccines were well tolerated. In healthy normal adults, a triple antigen hepatitis B vaccine containing S and pre-S antigens produced an enhanced immunologic response and was as effective as a 2- and 3-dose regimen.

Osteoporosis and apolipoprotein E genotype in older adults: the Rancho Bernardo study.

Recent studies reported an association between apolipoprotein E (ApoE) 4 and osteoporosis. We examined the association of ApoE 4 genotype with bone mineral density (BMD), bone loss and fracture risk in 596 men and 332 community-dwelling women aged 45-95 years. Women were postmenopausal and not using estrogen. At the baseline visit, BMD was measured at the ultradistal and midshaft radius using single photon densitometry, and at the hip and lumbar spine using dual-energy X-ray absorptiometry. Hip and lumbar spine BMD levels were remeasured 4 years later. Self-reported fractures were confirmed by radiology reports in 95% of cases. ApoE allele distribution did not vary by age; 25% of men and 20% of women had one ApoE 4 allele. There were no differences in BMD at the lumbar spine, total hip, ultradistal or midshaft radius in men or women with the ApoE 4 allele compared with men or women without the ApoE 4 allele. After an average 4 year interval, there were also no differences in the annualized percent change in BMD at the hip or lumbar spine in men or women with or without an ApoE 4 allele. One or more clinical fractures were reported by 55 men and 109 women. Fewer, not more, clinical fractures were reported in men and women with an ApoE 4 allele; these differences were not statistically significant (p = 0.21 and p = 0.62, respectively). These data do not support the hypotheses that there is an association between ApoE genotype and BMD, bone loss or osteoporotic fractures in older community-dwelling men or women.

Effects of lower doses of conjugated equine estrogens and medroxyprogesterone acetate on endometrial bleeding.

OBJECTIVE: To evaluate vaginal bleeding profiles with lower doses of conjugated equine estrogens (CEE) and medroxyprogesterone acetate (MPA) as continuous combined therapy. DESIGN: The Women's Health, Osteoporosis, Progestin, Estrogen (Women's HOPE) study, a randomized, double-blind, placebo-controlled trial. SETTING: Study centers across the United States. PATIENT(S): Two thousand six hundred seventy-three healthy, postmenopausal women. INTERVENTION(S): Women received CEE, 0.625 mg/d; CEE, 0.625 mg/d, plus MPA 2.5 mg/d; CEE, 0.45 mg/d; CEE, 0.45 mg/d, plus MPA, 2.5 mg/d; CEE 0.45 mg/d, plus MPA, 1.5 mg/d; CEE, 0.3 mg/d; CEE, 0.3 mg/d, plus MPA, 1.5 mg/d; or placebo for 1 year. MAIN OUTCOME MEASURE(S): Bleeding data were analyzed in efficacy-evaluable and intention-to-treat populations. RESULT(S): Cumulative amenorrhea and no bleeding rates were higher with lower doses of CEE/MPA than with CEE 0.625/MPA 2.5. A linear trend between time since menopause and cumulative amenorrhea was observed (P<.05) in all CEE/MPA groups except the CEE 0.45/MPA 1.5 group. The proportion of patients who experienced no bleeding in cycle 1 was 89%, 82%, and 80% in the CEE 0.3/MPA 1.5, CEE 0.45/MPA 1.5, and CEE 0.45/MPA 2.5 groups, respectively. These values were significantly greater than the incidence of no bleeding in the CEE 0.625/MPA 2.5 group (P<.05). CONCLUSION(S): Lower-dose regimens of CEE and MPA produce higher rates of amenorrhea and no bleeding compared with CEE 0.625/MPA 2.5 and may be appropriate for newly menopausal patients.

Vitamin C supplement use and bone mineral density in postmenopausal women.

Vitamin C is known to stimulate procollagen, enhance collagen synthesis, and stimulate alkaline phosphatase activity, a marker for osteoblast formation. Studies of dietary vitamin C intake and the relation with bone mineral density (BMD) have been conflicting, probably because of the well-known limitations of dietary nutrient assessment questionnaires. The purpose of this study was to evaluate the independent relation of daily vitamin C supplement use with BMD in a population-based sample of postmenopausal women. Subjects were 994 women from a community-based cohort of whom 277 women were regular vitamin C supplement users. Vitamin C supplement use was validated. Daily vitamin C supplement intake ranged from 100 to 5,000 mg; the mean daily dose was 745 mg. Average duration of use was 12.4 years; 85% had taken vitamin C supplements for more than 3 years. BMD levels were measured at the ultradistal and midshaft radii, hip, and lumbar spine. After adjusting for age, body mass index (BMI), and total calcium intake, vitamin C users had BMD levels approximately 3% higher at the midshaft radius, femoral neck, and total hip (p < 0.05). In a fully adjusted model, significant differences remained at the femoral neck (p < 0.02) and marginal significance was observed at the total hip (p < 0.06). Women taking both estrogen and vitamin C had significantly higher BMD levels at all sites. Among current estrogen users, those also taking vitamin C had higher BMD levels at all sites, with marginal significance achieved at the ultradistal radius (p < 0.07), femoral neck (p < 0.07), and total hip (p < 0.09). Women who took vitamin C plus calcium and estrogen had the highest BMD at the femoral neck (p = 0.001), total hip (p = 0.05), ultradistal radius (p = 0.02), and lumbar spine. Vitamin C supplement use appears to have a beneficial effect on levels of BMD, especially among postmenopausal women using concurrent estrogen therapy and calcium supplements.

Acute rejection-associated tubular basement membrane defects and chronic allograft nephropathy.

BACKGROUND: Acute rejection is a major risk factor for chronic allograft nephropathy, although the link(s) between these events is not understood. The hypothesis of this study is that alterations in tubular basement membranes (TBMs) that occur during acute rejection may be irreversible and thereby play a role in the development of chronic allograft nephropathy. METHODS: Fourteen renal transplant patients were selected, each having had two or more biopsies performed (42 total). All biopsies were scored for acute and chronic rejection using Banff 1997 criteria. The initial biopsy showed only acute interstitial rejection (type I rejection). No biopsies contained significant chronic arterial lesions of chronic vascular rejection. The entire cortex was examined on Jones methenamine silver-stained sections at x400 for interruption in TBM staining. The number of tubules with TBM abnormalities was counted, and the renal cortical area was measured by image analysis. Periodic acid-Schiff/immunoperoxidase stain was performed on 12 acute rejection biopsies stained for laminin, cytokeratin 7, CD3, CD20, and CD68. Controls consisted of 11 biopsies (8 negative for rejection and 3 acute tubular necrosis). RESULTS: Numerous TBM alterations in silver staining were identified as being associated with acute rejection and tubulitis, consisting of abrupt TBM discontinuities and/or extreme attenuation with segmental or complete absence of TBM. A loss of TBM matrix proteins was confirmed by absent laminin staining in areas of acute rejection and tubulitis. There was herniation of tubular cells into the interstitium through TBM defects confirmed by cytokeratin staining. The TBM defects were spatially associated with inflammatory cells, particularly macrophages. When the biopsies were divided into two groups, <10 and> 10 TBM breaks/mm2, there were statistically significant morphologic and clinical correlations. The number of TBM disruptions correlated with the serum creatinine at the time of biopsy, a combined Banff t + i score, the difference in tubular atrophy between the initial and most recent biopsy and the difference between the nadir creatinine and most recent creatinine. CONCLUSION: Damage to TBM develops in acute rejection as a consequence of interstitial inflammation and tubulitis. These lytic events correlate with the later development of clinical and morphologic evidence of chronic injury in the absence of arterial injury of chronic rejection. We suggest that chronic allograft nephropathy may have an inflammatory interstitial origin.

Hand ultrasound for osteoporosis screening in postmenopausal women.

There is a need for low-cost screening methods to detect low bone mass (osteopenia or osteoporosis) in postmenopausal women. The utility of quantitative ultrasonography (QUS) of the hand was assessed for osteoporosis screening using the WHO criteria. Bone mineral density (BMD) was measured in 206 postmenopausal Mexican-American women at the total hip and lumbar spine by dual-energy X-ray absorptiometry (DXA). The amplitude-dependent speed of sound (AD-SoS) was measured in the phalanges by QUS. Subjects identified by DXA as having osteopenia or osteoporosis had significantly lower AD-SoS values in comparison with normals. Estrogen users had significantly higher spine and hip BMD and AD-SoS values compared with non-estrogen users. The areas under the receiver operating characteristic (ROC) curves (AUC) for AD-SoS to screen for osteoporosis (T-score < or = -2.5) at the spine or hip were 0.73 for all subjects, 0.74 for estrogen users and 0.68 for non-estrogen users. The AUC for non-estrogen users to screen for osteopenia (T-score -1 to -2.5) was 0.77. Performance comparisons of AD-SoS with SCORE (a risk factor questionnaire) and body weight showed AUC values of 0.73, 0.69 and 0.65, respectively. QUS was the superior screening test when considering both the AUC and the shape of the ROC curves. For non-estrogen users, the group at higher risk for osteoporosis, QUS correctly identified 31% as normal, and 62% as having low bone mass and needing DXA referral; and the remaining 7% were false negatives. These data suggest phalangeal QUS can be effectively used for screening osteoporosis in postmenopausal women.

The contribution of testosterone to skeletal development and maintenance: lessons from the androgen insensitivity syndrome.

Although androgen status affects bone mass in women and men, an androgen requirement for skeletal normalcy has not been established. Women with androgen insensitivity syndrome (AIS) have 46,XY genotypes with androgen receptor abnormalities rendering them partially or completely refractory to androgen. Twenty-eight women with AIS (22 complete and 6 high grade partial), aged 11-65 yr, responded to questionnaires about health history, gonadal surgery, and exogenous estrogen use and underwent bone mineral density (BMD) assessment by dual energy x-ray absortiometry. BMD values at the lumbar spine and proximal femur were compared to age-specific female normative values and listed as z-scores. Average height for adults in this cohort, 174 cm (68.5 in.), was moderately increased compared with the average height of adult American women of 162.3 cm, with skewing toward higher values: 5 women exceeded 6 ft in height, and 30% of the 18 adult women with complete AIS exceeded 5 ft, 11 in. in height. The average lumbar spine and hip BMD z-scores of the 6 women with partial AIS did not differ from population norms. In contrast, the average lumbar spine BMD z-score of women with complete AIS was significantly reduced at -1.08 (P = 0.0003), whereas the average value for hip BMD did not differ from normal. When BMD was compared between women who reported good estrogen replacement therapy compliance and those who reported poor compliance, there was a significantly greater deficit at the spine for women with poor compliance (z = -2.15 +/- 0.15 vs. -0.75 +/- 0.28; P < .0001). Furthermore, hip BMD was also significantly reduced in the noncompliant group (z = -0.95 +/- .40). Comparison of BMD values to normative male standards gave z-score reductions (z = -1.81 +/- 0.36) greater than those observed with female standards. Because of the high prevalence of tall stature in this study sample, we calculated bone mineral apparent density, a variable that adjusts for differences in bone size. Even for the estrogen-compliant group, bone mineral apparent density z-scores were subnormal at both the spine (z = -1.3 +/- 0.43; P < 0.01) and the hip (z = -1.38 +/- 0.28; P = 0.017). Six women with complete AIS had sustained cortical bone fractures, of whom 3 reported multiple (>3) fractures. We conclude that even when compliance to exogenous estrogen use is excellent, women with complete AIS show moderate deficits in spine BMD, averaging close to 1 SD from normative means, and that with correction of BMD for bone size, skeletal deficits are magnified and include the proximal femur. The results suggest that severe osteopenia in some women with AIS probably reflects a component of inadequate estrogen replacement rather than androgen lack alone.

Low levels of estradiol are associated with vertebral fractures in older men, but not women: the Rancho Bernardo Study.

This longitudinal study included 288 postmenopausal women without estrogen use (median age, 72 yr) and 352 men (median age, 66 yr). All were community-dwelling, ambulatory, and Caucasian. Blood for hormone assays (total and bioavailable estradiol and testosterone, estrone, androstenedione, dihydrotestosterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate) was obtained in 1984-1987, and vertebral fractures were diagnosed from lateral spine radiographs obtained in 1992-1996. At least one vertebral fracture was found in 21% of women and 8% of men. Among men, age-adjusted hormone levels differed by fracture status only for total (64.1 vs. 75.4 pmol/L, P = 0.012) and bioavailable (43.0 vs. 51.4 pmol/L, P = 0.008) estradiol. There was a graded association between higher concentrations of total and bioavailable estradiol and lower fracture prevalence (trend P<0.01 for both hormones). Men with total testosterone levels compatible with hypogonadism (<7 nmol/L) were not more likely to have vertebral fractures. In women, none of the measured sex hormones was associated with vertebral fractures. There was also no increased prevalence of fractures in women with estradiol levels below the assay sensitivity (<11 pmol/L). These data suggest that estrogen plays a critical role in the skeletal health of older men and confirm other studies showing no association of postmenopausal endogenous estrogen levels with vertebral fractures in older women.

Cervicography screening for cervical cancer among 8460 women in a high-risk population.

OBJECTIVE: Cervicography was evaluated as a primary screening method for cervical cancer. STUDY DESIGN: Cervigrams of 8460 women were taken on enrollment into a population-based study of cervical neoplasia. Cervicography results were compared with a referent diagnosis determined by histologic analysis and 3 cytologic tests, and with the performance of conventional cytologic evaluation. RESULTS: Cervicography identified all 11 cancers, whereas cytologic testing missed 1. Cervicography yielded sensitivities for detecting high-grade squamous intraepithelial lesions or cancer of 49.3% overall (specificity, 95.0%), 54.6% in women younger than 50 years of age, and 26.9% in women 50 years of age and older. Cytologic testing yielded sensitivities for detecting high-grade squamous intraepithelial lesions or cancer of 77.2% overall (specificity, 94. 2%), 75.5% in women younger than 50 years of age, and 84.6% in women 50 years of age and older. CONCLUSIONS: Cytologic testing performed better than cervicography for the detection of high-grade squamous intraepithelial lesions. Cervicography performed marginally better than cytologic testing for the detection of invasive cervical cancer. Cervicography is not recommended for postmenopausal women.

Nonsteroidal anti-inflammatory drugs and bone mineral density in older women: the Rancho Bernardo study.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to inhibit synthesis of prostaglandins and may help prevent bone loss, but no study has shown the differential association of type or dose of NSAID compound with bone mineral density (BMD). The purpose of this study was to determine the relation of NSAIDs by type and dose to BMD. Participants were 932 Caucasian, community-dwelling women aged 44-98 years from southern California. Data were collected from 1988 to 1991 through the use of standardized medical questionnaires. Medication use was validated by a nurse. BMD at the ultradistal and midshaft radii were measured using single-photon absorptiometry, and at the hip and lumbar spine using dual-energy X-ray absorptiometry. Women (mean age, 72 years) were classified into 818 nonusers and 114 regular daily users of NSAIDs, of which 84 used propionic acid NSAIDs and the remainder used acetic acid NSAIDs. Occasional NSAID users were excluded. Women who used propionic acid NSAIDs, but not acetic acid NSAIDs, had higher BMD at all five sites and significantly higher BMD at the midshaft radius and lumbar spine. These differences remained after controlling for known covariates of osteoporosis. When women with self-reported osteoarthritis were excluded from the model, significantly higher BMD in propionic acid NSAID users was also observed at the femoral neck and total hip. Those who concurrently used estrogen and propionic acid NSAIDs had the highest BMD at all sites, suggesting an additive effect. We conclude that regular daily use of propionic acid NSAIDs, with or without simultaneous use of estrogen, may be helpful in preventing bone loss in older women. However, further research is needed to confirm these results before any clinical practice guidelines can be recommended due to the increased risk of serious complications associated with NSAID use.

Influence of insurance coverage on delays in seeking emergency care in patients with acute chest pain.

The time required to decide to seek medical care for acute chest pain is the major modifiable component in the process of care delivery. This study demonstrates that prehospital delay in the setting of acute chest pain was related to the type of health insurance.

Pitfalls in interpretation: calcium that's not bone.

This is a 65-yr-old woman with dermatomyositis and extensive calcinosis. On physical examination subcutaneous nodules were widely distributed on her chest and extremities. Her current CPK is 163 IU/L (normal range 0-175); however, with a recent flare of her symptoms, the CPK peaked at 411 IU/L. Her current medications are Imuran 25 mg/d, Prednisone 4 mg/d, and conjugated equine estrogen 0.625 mg/d.

Urinary N-telopeptide levels discriminate normal, osteopenic, and osteoporotic bone mineral density.

BACKGROUND: The level of urinary, type I collagen, crosslinked N-telopeptides (NTX) is a new marker of bone resorption. To our knowledge, no population-based studies of older adults have determined whether this measure can identify individuals with osteoporosis. OBJECTIVES: To measure the levels of NTX in a cross-sectional study of ambulatory, older, white adults and to evaluate whether this measure of bone resorption could identify individuals with osteoporosis. PATIENTS AND METHODS: The subjects, aged 50 to 98 years, formed 3 groups: 374 men, 223 women currently using estrogen, and 364 women not currently using estrogen. A standard medical history and validated record of medication use were obtained. Height and weight were measured. Bone mineral density (BMD) was measured at the hip and lumbar spine using dual energy x-ray absorptiometry. The levels of NTX were measured by enzyme-linked immunosorbent assay. RESULTS: Overall, the levels of NTX increased slightly with age in men and in estrogen users and more dramatically in nonestrogen users. In a model adjusted for all major risk factors for osteoporosis, there was a significant decrease in BMD levels by increasing quintiles of NTX levels at the hip and spine in women with and without estrogen use and at the hip in men. Using sex-specific, peak bone mass criteria and age-adjusted analyses, the levels of NTX discriminated between normal (< or = -1.0 SD), osteopenic (> -1.0 and < -2.5 SD), and osteoporotic (> or = -2.5 SD) BMD levels in all groups except the spine in men. CONCLUSIONS: The levels of NTX uniquely discriminated between older adults with normal, osteopenic, or osteoporotic BMD levels. If confirmed, these data suggest that NTX levels could be used to predict current osteoporosis in older men and women.

Timing of postmenopausal estrogen for optimal bone mineral density. The Rancho Bernardo Study.

OBJECTIVE: To determine the effect of the timing of initiation and the duration of postmenopausal estrogen therapy on bone mineral density (BMD). DESIGN: Cross-sectional study. SETTING: White, middle-class to upper middle-class community-dwelling women. PARTICIPANTS: A total of 740 women aged 60 to 98 years who participated in a study of osteoporosis. MEASUREMENTS: Questionnaire, validated medication use, and height and weight. Bone mineral density at the ultradistal radius and midshaft radius using single-photon absorptiometry (SPA) and at the hip and lumbar spine using dual-energy x-ray absorptiometry (DEXA). RESULTS: Of the 740 women, 69% had used oral estrogen after menopause and 30% were current users. Five groups of estrogen use were identified: never users, past users who started at menopause, past users who started after age 60 years, current users who started after age 60 years, and current users who started at menopause. At all 4 bone sites, current users who started at menopause had the highest BMD levels, which were significantly higher than never users or past users who started at menopause (with 10 years' duration of use). These differences persisted after controlling for all major risk factors for osteoporosis. Among current users, there was no significant difference in BMD levels at any site between those who started estrogen at menopause (with 20 years of use) and those who started after age 60 years (with 9 years of use). CONCLUSIONS: Estrogen initiated in the menopausal period and continued into late life is associated with the highest bone density. Nevertheless, estrogen begun after age 60 years and continued appears to offer nearly equal bone-conserving benefit.

The effect of noninsulin dependent diabetes mellitus on the prevalence of clinical osteoarthritis. A population based study.

OBJECTIVE: To explore the relation between noninsulin dependent diabetes mellitus (NIDDM) and osteoarthritis (OA) in a population. METHODS: The study population included 632 men and 882 women aged 52-95 years from the Rancho Bernardo community. In 1984-87, participants answered questions about history of diabetes and had a standard oral glucose tolerance (OGTT). In 1988-92, subjects completed a questionnaire about history of arthritis, type of arthritis diagnosed, and presence of joint pain. Nurses examined subjects for presence of Heberden's nodes. Subjects with no history of arthritis were compared to those with a history of OA and other types of arthritis with regard to age, body size, and plasma glucose levels. In addition, subjects were classified by diabetes status to determine differences in the prevalence of arthritis and related characteristics. RESULTS: Neither impaired glucose tolerance nor NIDDM was associated with history of OA, regardless of how inclusive the definition of OA, before or after adjustment for age and maximum lifetime obesity. In age and obesity adjusted analyses, men with a history of OA had lower fasting plasma glucose levels than men with no arthritis (100.2 vs. 103.6 mg/dl, p < 0.05), and men with NIDDM had less hand and hip pain than normoglycemic men (p < 0.05). Heberden's nodes were unrelated to glucose tolerance status. CONCLUSION: This population based study found no positive association between clinical OA and NIDDM defined by OGTT. These results are compatible with community based data examining radiographic OA and history of diabetes.

Thyroid hormone use and bone mineral density in elderly men.

BACKGROUND: Excessive thyroid hormone use reduces bone density in women. Thyroid hormone use is much less common in men, who also have less osteoporosis. We examined bone mineral density in a community-based sample of elderly men who reported long-term thyroid hormone use. METHODS: All 685 white men aged 50 to 98 years from a Southern California community who participated in a study of osteoporosis were examined. Medication use was validated. Height and weight were measured. Bone mineral density was measured at the ultradistal radius and midshaft radius using single photon absorptiometry and at the hip and lumbar spine using dual energy x-ray absorptiometry. RESULTS: Thirty-three men taking a mean thyroxine-equivalent dose of 130 micrograms daily for an average of 15.5 years were compared with 653 nonusers. There were no significant differences in bone density at any site between users and nonusers, before or after controlling for age, body mass index, smoking, thiazide diuretics, and oral corticosteroid use. Bone density also did not differ according to thyroid hormone type, duration of use, or use of suppressive dose adjusted for body weight. CONCLUSIONS: Long-term thyroid hormone use was not associated with adverse effects on bone mineral density in men.

Translocation of both lysosomal LDL-derived cholesterol and plasma membrane cholesterol to the endoplasmic reticulum for esterification may require common cellular factors involved in cholesterol egress from the acidic compartments (lysosomes/endosomes).

Using a stable cell line 25-RA derived from wild-type Chinese hamster ovary (CHO) cells as the parental cell, this laboratory previously reported the isolation and characterization of CHO cell mutants (cholesterol-trafficking or CT) defective in transporting LDL-derived cholesterol out of the acidic compartment(s) (lysosomes/endosomes) to the endoplasmic reticulum (ER) for esterification. In this report, we show that the CT mutation can be complemented by fusion with human cells; however, attempts to complement the CT defect through DNA transfection have resulted in a collection of stable cell lines designated as ST cells. Under cholesterol starvation condition, the ST cells exhibit an elevated rate of cholesterol ester biosynthesis (by 3- to 5-fold) compared to both the parental CHO cells and the CT cells. The phenotypes of the ST cells are stable. ST cells are thus new cell lines arisen from the CT cells. When the plasma membranes of the parental, CT, and ST cells are labelled with [3H]cholesterol, ST cells show rates of [3H]cholesterol esterification much higher than that observed in CT cells but lower than that observed in the parental CHO cells. This result shows that translocation of plasma membrane cholesterol to the ER for esterification is defective in the CT cells. This result also suggests that ST cells acquire increased cholesterol trafficking activity between the lysosome and the ER without mixing the plasma membrane cholesterol pool. The characteristics of CT cells and ST cells reported here suggest that translocation of both lysosomal LDL-derived cholesterol and plasma membrane cholesterol to the ER for esterification may require common cellular factors involved in cholesterol egress from the acidic compartment(s) (lysosomes/endosomes).