Spine In Women Research Articles

Inverse association of carotenoid intakes with 4-y change in bone mineral density in elderly men and women: the Framingham Osteoporosis Study

BackgroundIn vitro and in vivo studies suggest that carotenoids may inhibit bone resorption and stimulate proliferation and differentiation of osteoblasts. Few studies have examined the association between carotenoid intake (other than β-carotene) and bone mineral density (BMD). ObjectiveWe evaluated associations between total and individual carotenoid intake (α-carotene, β-carotene, β-cryptoxanthin, lycopene, and lutein+zeaxanthin) with BMD at the hip, spine, and radial shaft and the 4-y change in BMD. DesignBoth cross-sectional and longitudinal analyses were conducted in 334 men and 540 women (mean ± SD age: 75 ± 5 y) in the Framingham Osteoporosis Study. Energy-adjusted carotenoid intakes were estimated from the Willett food-frequency questionnaire. Mean BMD and mean 4-y BMD changes were estimated, for men and women separately, by quartile of carotenoid intake with adjustment for age, BMI, height, physical activity index, smoking (never compared with ever smokers), multivitamin use, season of BMD measurement (for cross-sectional analyses on BMD only), estrogen use (in women), and intakes of total energy, calcium, vitamin D, caffeine, and alcohol. ResultsFew cross-sectional associations were observed with carotenoid intake. Associations between lycopene intake and 4-y change in lumbar spine BMD were significant for women (P for trend = 0.03), as were intakes of total carotenoids, β-carotene, lycopene and lutein+zeaxanthin with 4-y change in trochanter BMD in men (P for trend = 0.0005, 0.02, 0.009, and 0.008, respectively). ConclusionsCarotenoids showed protective associations against 4-y loss in trochanter BMD in men and in lumbar spine in women. No significant associations were observed at other bone sites. Although not consistent across all BMD sites examined, these results support a protective role of carotenoids for BMD in older men and women.

Influence of modified transdermal hormone replacement therapy on the concentrations of hormones, growth factors, and bone mineral density in women with osteopenia

The metabolic and therapeutic action of estrogens depends on their type, dosage, form, route of administration, and treatment-free interval during the therapeutic cycle. Hormone therapy is generally subclassified into 2 forms that differ in the type of hormones. In hormonal replacement therapy (HRT), estrogens and progesterone components do not differ in chemical structure and molecular mass from those naturally produced by the female organism. In hormonal supplementary therapy (HST), the estrogen and progestagen components do differ from the natural hormones in structure and mass. The aim of the study was to compare 2 kinds of hormonal therapy in early postmenopausal women with osteopenia. These forms of therapy are modified transdermal HRT and orally given HST. The objective of this study was the estimation of sex hormone, insulin-like growth factor I (IGF-I), prolactin (PRL), osteocalcin, and procollagen concentration in serum as well as the degree of mineralization of the lumbar spine in women in the early postmenopausal period with osteopenia under different kinds of hormonal therapy. The study was conducted in 75 women with an average age of 52.4 ± 3.5 years and with primary osteopenia, in the early postmenopausal period, who were randomly assigned to 3 groups depending on the form and route of administration of therapy: Group I (n = 25, control) was receiving placebo in the form of patches. Group II (n = 25) was treated with modified transdermal HRT. This group obtained micronized 17 β-estradiol at increasing-decreasing doses and progesterone in the second phase of the therapeutic cycle. Group III (n = 25) was receiving orally given HST and obtained Cyclo-Menorette (Wyeth, Munster, Germany). The therapeutic cycle in each group lasted 21 days, followed by a 7-day medication-free interval. Estradiol concentration in serum was increased 5-fold and estrone (E 1) was increased about 11-fold in the group of women receiving orally given HST ( P < .0001) compared with control group. Estrone and estradiol levels were increased about 3-fold in women receiving modified transdermal HRT compared with the baseline values. Basal PRL concentration and PRL level after metoclopramide stimulation test significantly increased after 3 and 12 months of treatment in the group receiving orally given HST. In women receiving modified transdermal HRT, increased IGF-I concentrations were statistically significant after 3 months of treatment. In the group of women receiving orally given HST, a significant decrease of IGF-I after 1 year therapy was found. During the entire time of treatment in this group, an increase of growth hormone was observed. No significant changes were shown in osteocalcin and in carboxyterminal propeptide of type I procollagen in all groups. Increase in bone mineral density L 2-L 4 was statistically significant in the group receiving modified transdermal HRT ( P < .01) and was insignificant in women receiving orally given HST after 12 months of therapy as compared with baseline values. Following are the conclusions: (1) Low-dose modified transdermal HRT modulates concentration of hormones, growth factor, IGF-I, osteocalcin, procollagen, and bone metabolism. (2) The curve concentrations of estrogens and progesterone in serum are similar to the type observed in the physiologic menstrual cycle. (3) The lack of significant increase in bone mineral density of lumbar spine in women after HST may be a result of significantly lower concentration of IGF-I in serum and occurring hyperprolactinemia.

Epidemiology of lumbar osteoporosis and osteoarthritis and their causal relationship—is osteoarthritis a predictor for osteoporosis or vice versa?: The Miyama study

In a 10-year follow-up of a population-based cohort of Japanese subjects, incidences of and causal relationships between osteoporosis (OP) and osteoarthritis (OA) at the lumbar spine were clarified. OP might reduce the risk of subsequent OA at the spine in women, but not in men. The aim of this study is to clarify the contribution of osteoarthritis (OA) to osteoporosis (OP) and vice versa. A population-based, epidemiological study was conducted in a Japanese rural community. From 1,543 participants aged 40-79 years, 200 men and 200 women were selected and followed up for 10 years. Bone mineral density measurements were repeated after 3, 7, and 10 years, and X-rays were repeated after 10 years. The incidence of lumbar OP per 10,000 person-years for persons in their 40s, 50s, 60s, and 70s was 0, 0, 109.5, and 151.1 for men and 124.2, 384.0, 227.3, and 239.5 for women, respectively. The cumulative incidence of lumbar OA over 10 years aged 40-79 years was 25.8% in men and 45.2% in women. Cox's proportional hazards model showed no significant relationship between the presence of lumbar OA at the baseline and incidence of lumbar and femoral neck OP in both genders. A significant relationship was demonstrated between the presence of lumbar OP, not femoral neck OP, at the baseline and cumulative incidence of lumbar OA in women (odds ratio, 0.20; 95% confidence interval, 0.05-0.80; P = 0.02). OP in women appears to reduce the future incidence of OA at the lumbar spine.

Association of genetic variants of MAOA and SH2B1 with bone mineral density in community-dwelling Japanese women

Although bone mineral density (BMD) is a complex trait that is influenced by both genetic and environmental factors, heritability studies in twins and families have shown that genetic factors account for 60-85% of its variance. We examined the relation of the variable number of tandem repeats (VNTR) polymorphism of the monoamine oxidase A gene (MAOA) and the A↷G (Thr484Ala) polymorphism of the SH2B adaptor protein 1 gene (SH2B1) to BMD in community-dwelling Japanese women and men. The 2235 subjects (1107 women, 1128 men) were aged 40-79 years and were randomly recruited for a population-based prospective cohort study of aging and age-related diseases in Japan. BMD at the distal and proximal radius was measured by peripheral quantitative computed tomography, and the BMD of the total body, lumbar spine (L2-L4), right femoral neck and right trochanter was measured by dual-energy X-ray absorptiometry. The genotypes of the VNTR polymorphism of MAOA were determined by DNA fragment analysis, and those of the A↷G (Thr484Ala) polymorphism of SH2B1 by melting curve analysis. The VNTR polymorphism of MAOA was associated with the BMD of the distal radius, total body, lumbar spine and trochanter in all women, and with the BMD of the total body and trochanter in postmenopausal ones, with the L (four repeats) and S (two or three repeats) alleles reflecting increased and decreased BMD, respectively. The A↷G (Thr484Ala) polymorphism of SH2B1 was associated with the BMD of the lumbar spine in all women, with the BMD of the proximal radius in premenopausal women and with the BMD of the lumbar spine, femoral neck and trochanter in postmenopausal women, with the variant G allele being related to increased BMD. These results suggest that MAOA and SH2B1 are determinative loci for bone mass in Japanese women, especially in postmenopausal ones.

Association between osteoprotegerin (OPG), receptor activator of nuclear factor-κB (RANK), and RANK ligand (RANKL) gene polymorphisms and circulating OPG, soluble RANKL levels, and bone mineral density in Korean postmenopausal women

To investigate the association between osteoprotegerin (OPG), receptor activator of nuclear factor-kappaB (RANK), and RANK ligand (RANKL) gene polymorphisms and circulating OPG, soluble RANKL (sRANKL) levels, and bone mineral density (BMD) in Korean postmenopausal women. The OPG gene A163G, G209A, T245G, and G1181C polymorphisms, the RANK gene C421T and C575T polymorphisms, and the RANKL rs12721445 and rs2277438 polymorphisms were analyzed in 385 Korean postmenopausal women. Levels of serum OPG, soluble RANKL, osteocalcin, C-telopeptide of type I collagen, parathyroid hormone, calcium, and phosphorus and BMD at the lumbar spine and femoral neck were measured. The A163G, G209A, and T245G polymorphisms in the OPG gene were in complete linkage. The RANK C421T and C575T polymorphisms and the RANKL rs12711445 polymorphism were not observed. An association with BMD was found only for the OPG G1181C polymorphism, and BMD at the lumbar spine in women with the CC genotype was significantly higher than in women with the GC or GG genotype, with a C allele dose effect. In itself, the RANKL rs2277438 polymorphism was not related to BMD, but by combining the RANKL genotypes with the GC genotypes of the OPG G1181C polymorphism, the association with BMD at the lumbar spine became significant. No significant differences in the levels of any biochemical marker among genotypes of these polymorphisms were found. The OPG gene G1181C polymorphism, alone and in combination with the RANKL rs2277438 polymorphism, was identified as a genetic factor associated with BMD of the lumbar spine in Korean women.

The sex-specific association of serum osteoprotegerin and receptor activator of nuclear factor κB legend with bone mineral density in older adults: the Rancho Bernardo Study

The role of osteoprotegerin (OPG) and its receptor activator of nuclear factor kappaB legend (RANKL) in the regulation of bone in humans remain unclear. We examined the sex-specific associations of serum OPG, RANKL, and their ratio with bone mineral density (BMD) in older adults. Participants were 681 community-dwelling adults, ages 45-90 years, who had serum OPG and RANKL measured and bone density scans in 1988-1991, with follow-up scans 5 and/or 10 years later. Analyses were sex-specific; women using and not using estrogen were evaluated separately. Cross-sectional analyses used multivariable regression models; longitudinal analyses used repeated measures mixed effects models. In cross-sectional analyses, age- and weight-adjusted serum OPG levels were significantly positively associated with BMD at the lumbar spine in men, and at the femoral neck, total hip, and lumbar spine in women using estrogen, but not in non-users of estrogen. RANKL concentrations were significantly and inversely associated with BMD in men only, and at the total hip. Neither OPG nor RANKL was significantly associated with bone loss. Results for the RANKL/OPG ratio were the same as those for RANKL alone. These results suggest a modulatory effect of both endogenous and exogenous sex hormones on the biologic interaction of OPG, RANKL, and bone.

Association of estrogen receptor α gene polymorphisms with bone mineral density in Chinese women: a meta-analysis

A large number studies have examined the association between estrogen receptor alpha (ESR-alpha) gene polymorphisms and bone mineral density (BMD) in the Chinese population. We conducted a meta-analysis to assess their pooled effects. We searched for all published articles indexed in MEDLINE, the Chinese Biomedical Database, and the Chinese Journal Full-text Database from January 1994 to April 2006. Any cross-sectional study that tested the association between ESR-alpha PvuII or XbaI genotypes and BMD at the femoral neck or spine in Chinese women was included in the review. Data were extracted independently by two reviewers using a standardized data extraction form. Sixteen eligible studies involving 4,297 Chinese women were identified. The overall frequencies of X and P alleles were 28% and 40%, respectively. The PvuII polymorphism was statistically significantly associated with BMD at the femoral neck (P = 0.038 for PP = Pp = pp) but not at the lumbar spine in all women. The BMD difference for the contrasts of PP versus Pp/pp genotypes was -0.0105 (95%CI, -0.0202 approximately -0.0008) g/cm(2) (P = 0.036). The XbaI polymorphism was not associated with BMD at the femoral neck or lumbar spine. The PvuII polymorphism had a very weak association with femoral neck BMD whereas XbaI polymorphism was unlikely to be a predictor of femoral neck or spine BMD in Chinese women.

Daily and Cyclic Parathyroid Hormone in Women Receiving Alendronate

Parathyroid hormone (PTH), unlike antiresorptive agents, which lessen bone remodeling, initially stimulates bone formation and later promotes remodeling. Recent findings pose a question of efficacy when administering PTH with alendronate whether or not women have been previously treated for osteoporosis. This study was designed to show whether PTH treatment can improve bone mineral density (BMD) and biochemical markers of bone turnover in women who had received, and were still receiving, alendronate. A regimen consisting of 3-month cycles of PTH treatment alternating with 3-month periods of no PTH was compared with daily treatment. A total of 126 women with osteoporosis who had taken alendronate for at least 12 months were randomized to continued alendronate plus PTH (1–34), self-injected subcutaneously each day; continued alendronate plus cyclical PTH treatment; or alendronate alone for 15 months. The dose of alendronate was 70 mg weekly and that of PTH was 25 μg daily whether given cyclically or continuously. Calcium and vitamin D were given when needed. Markers of bone formation increased with daily PTH but did not change significantly in alendronate-treated women. After 15 months, BMD at the lumbar spine had increased 6.1% in women given daily PTH and 5.4% in those given cyclical PTH. It did not change significantly in alendronate-treated patients. All but 15% of women given PTH had an increase in spinal BMD. Changes in biochemical markers and spinal BMD did not correlate with the duration of previous alendronate treatment. BMD at the hip increased slightly in all groups. In no group was there a significant change in total-body BMD. The rate of new or worsening vertebral deformities was 3% in women given daily PTH, 6% in those receiving cyclical PTH, and 1% in those on alendronate. None of the women required dose reduction because of side effects. These findings suggest that cyclical PTH treatment for 3-month periods with 3-month periods off PTH, like daily treatment, increases BMD in the spine in women who continue to have osteoporosis after receiving alendronate. Cyclical PTH has results similar to those achieved with daily treatment but at a lesser cost.

Ratio of n–6 to n–3 fatty acids and bone mineral density in older adults: the Rancho Bernardo Study

Several lines of evidence suggest that n-3 fatty acids reduce the risk of some chronic diseases, including heart disease, diabetes, and cancer. Other research, mainly in animals, also suggests a role in bone health. We aimed to investigate the association between the ratio of dietary n-6 to n-3 fatty acids and bone mineral density (BMD) in 1532 community-dwelling men and women aged 45-90 y. Between 1988 and 1992, dietary data were obtained through self-administered food-frequency questionnaires, and BMD was measured at the hip and spine with the use of dual-energy X-ray absorptiometry. A medical history was obtained and current medication use was validated. Age- and multiple-adjusted linear regression analyses were performed. There was a significant inverse association between the ratio of dietary linoleic acid to alpha-linolenic acid and BMD at the hip in 642 men, 564 women not using hormone therapy, and 326 women using hormone therapy; these results were independent of age, body mass index, and lifestyle factors. An increasing ratio of total dietary n-6 to n-3 fatty acids was also significantly and independently associated with lower BMD at the hip in all women and at the spine in women not using hormone therapy. A higher ratio of n-6 to n-3 fatty acids is associated with lower BMD at the hip in both sexes. These findings suggest that the relative amounts of dietary polyunsaturated fatty acids may play a vital role in preserving skeletal integrity in older age.

The effects of phytoestrogen isoflavones on bone density in women: a double-blind, randomized, placebo-controlled trial

Isoflavone phytoestrogen therapy has been proposed as a natural alternative to hormone replacement therapy (HRT). HRT has a beneficial effect on bone, but few trials in humans have investigated the effects of isoflavones on bone. The objective of the study was to determine the effect on bone density of a red clover-derived isoflavone supplement that provided a daily dose of 26 mg biochanin A, 16 mg formononetin, 1 mg genistein, and 0.5 mg daidzein for 1 y. Effects on biochemical markers of bone turnover and body composition were also studied. Women aged 49-65 y (n = 205) were enrolled in a double-blind, randomized, placebo-controlled trial; 177 completed the trial. Bone density, body composition, bone turnover markers, and diet were measured at baseline and after 12 mo. Loss of lumbar spine bone mineral content and bone mineral density was significantly (P = 0.04 and P = 0.03, respectively) lower in the women taking the isoflavone supplement than in those taking the placebo. There were no significant treatment effects on hip bone mineral content or bone mineral density, markers of bone resorption, or body composition, but bone formation markers were significantly increased (P = 0.04 and P = 0.01 for bone-specific alkaline phosphatase and N-propeptide of collagen type I, respectively) in the intervention group compared with placebo in postmenopausal women. Interactions between treatment group and menopausal status with respect to changes in other outcomes were not significant. These data suggest that, through attenuation of bone loss, isoflavones have a potentially protective effect on the lumbar spine in women.

Does low bone mineral density start in post-teenage years in women with type 1 diabetes?

Type 1 diabetes has been associated with decreased bone mineral density (BMD). However, the natural history and etiopathogenesis of osteoporosis in type 1 diabetes are not clear. The aims of this study were to assess BMD in a cohort of young women with type 1 diabetes compared with nondiabetic control subjects and to evaluate the possible association of BMD with diabetes duration, HbA(1c), and biomarkers of bone metabolism. BMD was measured by dual-energy X-ray absortiometry scan in 39 teenage (age 13-19 years) and 33 post-teenage females (age 20-37 years) with type 1 diabetes and 91 female age-matched control subjects. Serum osteocalcin, IGF-I, IGF binding protein-3 (IGFBP-3), HbA(1c), and urine N-telopeptides were measured. After adjustment for age and BMI, BMD values were significantly lower at the femoral neck and lateral spine in women with type 1 diabetes older than age 20 years compared with control subjects but not in the case subjects younger than age 20 years, nor at the anterio-posterior spine, wrist, or whole body. No association was found between BMD and diabetes duration or glycemic control. IGF-I, IGFBP-3, osteocalcin, and N-telopeptides were similar in diabetic subjects and control subjects. This study indicates that women with type 1 diabetes exhibit BMD differences early in life with significant differences already present in the post-teenage years. Lower hip BMD in these young women may explain, in part, the higher incidence of hip fracture experienced in postmenopausal women with type 1 diabetes.

Digital X-ray radiogrammetry predicts hip, wrist and vertebral fracture risk in elderly women: a prospective analysis from the study of osteoporotic fractures.

Digital X-ray radiogrammetry (DXR) is a technique that uses automated image analysis of standard hand radiographs to estimate bone mineral density (DXR-BMD). Previous studies have shown that DXR-BMD measurements have high precision, are strongly correlated with forearm BMD and are lower in individuals with prevalent fractures. To determine whether DXR-BMD measurements predict wrist, hip and vertebral fracture risk we conducted a case-cohort study within a prospective study of 9704 community-dwelling elderly women (the Study of Osteoporotic Fractures). We compared DXR-BMD, and BMD of the radius (proximal and distal), calcaneus, femoral neck and posteroanterior lumbar spine in women who subsequently suffered a wrist (n = 192), hip (n = 195), or vertebral fracture (n = 193) with randomly selected controls from the same cohort (n = 392-398). DXR-BMD was estimated from hand radiographs acquired at the baseline visit. The radiographs were digitized and the Pronosco X-posure System was used to compute DXR-BMD from the second through fourth metacarpals. Wrist fractures were confirmed by radiographic reports and hip fractures were confirmed by radiographs. Vertebral fractures were defined using morphometric analysis of lateral spine radiographs acquired at baseline and an average of 3.7 years later. Age-adjusted odds ratio (OR, vertebral fracture) or relative hazard (RH, wrist and hip fracture) for a 1 SD decrease in BMD were computed. All BMD measurements were similar for prediction of wrist (RH = 1.5-2.1) and vertebral fracture (OR = 1.8-2.5). Femoral neck BMD best predicted hip fracture (RH = 3.0), while the relative hazards for all other BMD measurements were similar (RH = 1.5-1.9). These prospective data indicate that DXR-BMD performs as well as other peripheral BMD measurements for prediction of wrist, hip and vertebral fractures. Therefore, DXR-BMD may be useful for prediction of fracture risk in clinical settings where hip BMD is not available.

Number of years since menopause: spontaneous bone loss is dependent but response to hormone replacement therapy is independent

In this study we examine the influence of number of years since menopause on spontaneous bone loss and response to hormone replacement therapy (HRT) in 274 women (56.1 ± 4.2 years) completing two placebo-controlled HRT studies of 2 or 3 year duration. Both cross sectionally and longitudinally, bone loss in untreated women was greatest closest to menopause and declined thereafter ( r = 0.34, p < 0.01 for lumbar spine bone loss and r = 0.25, p < 0.05 for femoral neck bone loss when correlated with number of years since menopause), such that the loss was eliminated in the femoral neck and bone mass increased in the spine in women >10 years after menopause. In contrast, bone turnover was consistently elevated throughout postmenopause, both cross-sectionally and longitudinally. The association with number of years since menopause was counteracted by both 1 and 2 mg estradiol combined with gestodene, piperazine, estrone sulfate in combination with norethisterone, and a combination of 2 mg estradiol and 1 mg norethisterone acetate. In addition, the response to various HRT regimens was independent of baseline bone mass. Whereas bone loss was significantly related to number of years since menopause, all HRT regimens applied arrested bone loss in healthy postmenopausal women, regardless of number of years since menopause.

Depression, falls, and risk of fracture in older women. Study of Osteoporotic Fractures Research Group.

Previous studies have suggested that depression is associated with falls and with low bone density, but it is not known whether depression leads to an increased risk of fracture. We conducted a prospective cohort study in elderly white women who were recruited from population-based listings in the United States. At a second visit (1988-1990), 7414 participants completed the 15-item Geriatric Depression Scale and were considered depressed if they reported 6 or more symptoms of depression. We measured bone mineral density (BMD) in the spine and hip using dual energy x-ray absorptiometry at the second visit, and asked participants about incident falls (yes/no) at 4 follow-up visits. Nonvertebral fractures were ascertained for an average of 6 years following the depression measure, and verified radiologically. We determined incident vertebral fractures by comparing lateral spine films obtained at the first visit (1986-1988) with repeat films obtained an average of 3.7 years later (1991-1992). The prevalence of depression (Geriatric Depression Scale score > or = 6) was 6.3% (467/7414). We found no difference in mean BMD of the hip and lumbar spine in women with depression compared with those without depression. Women with depression were more likely to experience subsequent falls than women without depression (70% vs 59%; age-adjusted odds ratio [OR], 1.6; 95% confidence interval [CI], 1.3-1.9; P<.001), an association that persisted after adjusting for potential confounding variables (OR, 1.4; 95% CI, 1.1-1.8; P=.004). Women with depression had a 40% (age-adjusted hazard ratio [HR], 1.4; 95% CI, 1.2-1.7; P<.001) increased rate of nonvertebral fracture (124 fractures in 3805 woman-years of follow-up) compared with women without depression (1367 fractures in 59 503 woman-years of follow-up). This association remained strong after adjusting for potential confounding variables, including medication use and neuromuscular function (HR, 1.3; 95% CI, 1.1-1.6; P=.008). Further adjustment for subsequent falls appeared to explain part of this association (HR, 1.2; 95% CI, 1.0-1.5; P = .06). Women with depression were also more likely to suffer vertebral fractures than women without depression, adjusting for history of vertebral fracture, history of falling, arthritis, diabetes, steroid use, estrogen use, supplemental calcium use, cognitive function, and hip BMD (OR, 2.1; 95% CI, 1.4-3.2; P<.001). Depression is a significant risk factor for fracture in older women. The greater frequency of falls among individuals with depression partially explains this finding. Other mechanisms responsible for the association between depression and fracture remain to be determined.

Cross sectional investigation of the effects of inhaled corticosteroids on bone density and bone metabolism in patients with asthma.

BACKGROUND: Bone mineral density has been reduced in patients with asthma taking inhaled corticosteroids in some cross sectional studies and this could be important if treatment is continued for several...

Urinary N-Telopeptide Levels Discriminate Normal, Osteopenic, and Osteoporotic Bone Mineral Density

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. 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. 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. 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. 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.

Decreased serum IGF-I and dehydroepiandrosterone sulphate may be risk factors for the development of reduced bone mass in postmenopausal women with endogenous subclinical hyperthyroidism.

Postmenopausal women with endogenous subclinical hyperthyroidism seem to have reduced bone mass, which does not correlate with serum thyroid hormone levels. Relative insufficiencies of IGF-I and dehydroepiandrosterone sulphate (DHEAS) might be additional risk factors for low bone density in these patients. We measured IGF-I, IGF-binding protein-3 (IGFBP-3) and DHEAS levels together with bone mineral density (BMD) of the femoral neck and lumbar spine in women with an autonomously functioning thyroid nodule. Sixty-three women were classified as subclinical hyperthyroid (31 pre- and 32 postmenopausal) and 39 as overt hyperthyroid (16 pre- and 23 postmenopausal) and results were compared with data obtained from 41 age-matched euthyroid healthy women. In premenopausal women BMD was reduced only in the overt hyperthyroid group, and only in the spine, to 92% (P < 0.05). Serum IGF-I as well as IGFBP-3 were increased in the manifest hyperthyroid group, to 157% (P < 0.001) and 129% (P < 0.05) respectively, whereas DHEAS levels did not change in either premenopausal patient group. In postmenopausal women BMD was significantly reduced both in the subclinical hyperthyroid group (spine to 90% and femoral neck to 88%; P < 0.05), as well as in the hyperthyroid group (spine to 78% and femoral neck to 86%; P < 0.01). In contrast to premenopausal women, serum IGF-I and IGFBP-3 did not change in the two groups who were postmenopausal and serum DHEAS levels were reduced to 58% (P < 0.001) in both postmenopausal groups with subclinical as well as overt hyperthyroidism. In the same two groups of patients, serum IGF-I and DHEAS levels correlated with BMD (femoral neck; both r = 0.50, P < 0.05). In conclusion, women with a solitary autonomous thyroid nodule with subclinical hyperthyroidism have reduced BMD only if they are postmenopausal. This is probably due to the effect of subtle increases in thyroid hormone production together with lack of oestrogen protection of the skeleton. But additional risk factors for the development of enhanced bone loss might be a state of relative IGF-I and DHEAS insufficiency in these patients as well as in postmenopausal women with overt hyperthyroidism.

Growth hormone and the acquisition of bone mass.

Bone remodelling is a continuous, closely coupled process of bone resorption followed by bone formation. This process is regulated by factors and hormones which include GH, IGF-I and gonadal steroids. GH deficiency in childhood results in short stature and delayed bone maturation and a reduced peak bone mass might account for reduced BMC and BMD. Possible pathophysiological mechanisms for reduced bone mass in both childhood- and adult-onset GH deficiency are discussed. GH treatment effects on bone metabolism include increased remodelling, with increases in BMC, BMD and bone area. Increases in BMC and BMD are delayed while these changes are incorporated into the skeleton. BMC increases to a greater extent than BMD. At a cellular level, GH and IGF-I have direct and indirect effects on osteoblast and osteoclast precursors and fully differentiated cells. Osteoblasts possess both oestrogen and androgen receptors and bone loss accelerates with the loss of gonadal function. There are gender differences in GH effects on bone. BMD is related to fracture risk in the hip and lumbar spine in women. GH treatment might decrease fracture risk at a level comparable to oestrogen or bisphosphonate treatment. Patients with the lowest BMD prior to treatment derive the greatest benefit from GH therapy.

Rate of bone loss from lumbar spine in women with distal forearm fracture

Women who sustain a distal forearm fracture are at increased risk of vertebral osteoporosis, particularly if it occurs before the age of 60.1 The aim of this study was to determine the mechanism for low bone mineral density in the lumbar spine of these women by prospectively evaluating the rate of bone loss from the spine. From our previous study population,1 we studied 86 (69%) of the women (aged 50-81) who had sustained a distal forearm fracture between six months and three years before baseline and 297 women from an age matched, population based cohort. These women did not differ from those lost to follow up in their age, weight, height, years after menopause, or baseline bone mass of the lumbar spine. We measured bone mineral density by dual energy x ray absorptiometry (Lunar DPX, Lunar Corporation, Madison, WI, USA) at baseline and after two years. We examined the effect of age on bone mineral density by linear regression analysis and compared regression lines by …

Osteoporosis in treated adult coeliac disease.

Forty five women and 10 men with coeliac disease diagnosed in adult life, who were already on a gluten free diet, had serial bone mineral density measurements at the lumbar spine and femoral neck over 12 months. Osteoporosis, defined as a bone mineral density (BMD) < or = 2 SD below the normal peak bone mass was found in 50% of male and 47% of female coeliac patients. Patients with a BMD < or = 2 SD below age and sex matched normal subjects, had a significantly lower body mass index (21.3 kg.m-2 compared with 25.2 kg.m-2, p < 0.02 Wilcoxon rank sum test) and lower average daily calcium intake (860 mg/day compared with 1054 mg/day, p < 0.05 Wilcoxon rank sum test) than patients with normal bone mineral density. In postmenopausal women with coeliac disease there was a strong correlation between the age at menopause and BMD at both the lumbar spine (r = 0.681, p < 0.01, Spearman's rank correlation) and femoral neck (r = 0.632, p < 0.01). No overall loss of bone was shown over the 12 months of follow up, and relative to the reference population there was a significant improvement in BMD at the lumbar spine in women (p < 0.025, paired t test) and at the femoral neck in men (p < 0.05, paired t test). There was a significant negative correlation between the annual percentage change in BMD at the lumbar spine and the duration of gluten free diet (r = -0.429, p<0.01, Spearman's rank correlation), with the largest gain in BMD in patients with most recently diagnosed coeliac disease. Osteoporosis was shown in 47% of patients with treated adult coeliac disease. Recognised risk factors for osteoporosis in the general population including low body mass index, dietary calcium intake, and early menopause are particularly important in coeliac disease. Treatment of coeliac disease with a gluten free diet probably protects against further bone loss, and in the early stages is associated with a gain in bone mineral density.