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B L Riggs

Publications and source records attributed to B L Riggs.

At least 73 records · Page 4Linked to original sources
PubMed1998

Influence of fracture criteria on the outcome of a randomized trial of therapy.

Based on a presumption that the morphometric approach to vertebral fracture assessment is beset by false positive deformities, it has been suggested that more stringent criteria should be used to asses vertebral fracture outcomes in clinical trials of osteoporosis therapies. We applied a variety of criteria in the reanalysis of a randomized trial of sodium fluoride therapy for women with established osteoporosis. Although progressively more severe criteria reduced the cumulative incidence of a new vertebral fracture in both those receiving a placebo and the fluoride-treated patients, differences between the two groups were not magnified and none of the suggested approaches produced a statistically significant result. These findings indicate that the false positive rate associated with morphometric assessment of vertebral fractures is not so great as supposed from theoretical considerations that assume independence among the measurements. Our findings also provide some reassurance that differences in the criteria used to define a vertebral fracture are not the controlling influence in the likelihood that a particular clinical trial will find a result favoring one treatment over another.

Aged↗
PubMed1998

Estrogen effects on insulin-like growth factor gene expression in a human osteoblastic cell line with high levels of estrogen receptor.

Insulin-like growth factors (IGF)-I and IGF-II are produced by osteoblasts and are important paracrine/autocrine regulators of osteoblast proliferation and differentiation. Estrogen has been reported to increase gene expression of IGF-I in rodent osteoblasts. However, because species differences have been demonstrated in expression of various aspects of the IGF system in bone cells, it is not known whether this action also occurs in human osteoblasts. Thus, we assessed the effects of estrogen treatment on IGF-I and IGF-II gene expression in vitro in a recently developed human fetal osteoblast cell line that has high levels of estrogen receptors. As assessed by a quantitative reverse transcriptase-polymerase chain reaction method, treatment of hFOB/ER9 cells with 17beta-estradiol (E2) increased steady state levels of IGF-I mRNA in a time- and dose- dependent fashion with a maximal increase of 319% +/- 33% (P < 0.01) of control occurring after treatment with 10(-7) M E2 for 48 hours. In contrast, E2 did not alter steady state levels of IGF-II mRNA. The pure (type 2) antiestrogens ICI 182,780 (10(-7) M) and ICI 164,384 (10(-6) M) blocked the E2- induced increase in IGF-I mRNA levels. Interestingly, 4-hydroxytamoxifen (10(-7) M), a documented pure antiestrogen in reproductive tissues, also increased IGF-I mRNA to levels similar to those observed in E2-treated cells. Since E2 was shown to mediate its effects on some target genes through a cAMP-dependent pathway, we studied the interaction between E2 and agents that are known to increase intracellular cAMP. Forskolin (10(-8) M) and dibutyryl cAMP (10(-3) M) increased IGF-I mRNA levels sixfold, and cotreatment with E2 did not affect these changes, consistent with a possible mediation of the estrogen effect on IGF-I gene expression by cAMP. We conclude that in human osteoblastic cells, the IGF-I gene is a target for estrogen action, suggesting that IGF-I may mediate part of the effects of estrogen in human bone.

Bucladesine↗
PubMed1998

Estrogen regulation of a transforming growth factor-beta inducible early gene that inhibits deoxyribonucleic acid synthesis in human osteoblasts.

This laboratory reported the identification and characterization of a unique three zinc finger, transcription factor-like, transforming growth factor-beta inducible early gene (TIEG) (see Ref. 35). TIEG expression has been shown to be tissue- and cell type specific, enhanced by specific growth factors, and to decrease with advancing stages of breast cancer. Recent studies involving TIEG overexpression in pancreatic carcinoma cells indicate that TIEG expression inhibits DNA synthesis, similar to a tumor suppressor-like gene, and plays a role in apoptosis (see Ref. 37). This paper describes the rapid, but transient, induction of TIEG steady-state messenger RNA (mRNA) levels by 17beta-estradiol (E2) in estrogen receptor (ER)-positive, human fetal osteoblastic (hFOB/ER) cells. This rapid induction is shown to be ER- and steroid dose-dependent but protein synthesis independent. An antagonism between E2 and PTH, which occurs in skeletal metabolism, is shown to concur rapidly with TIEG mRNA expression. Scanning confocal microscopy (using polarized, laser-based immunofluorescence) shows that TIEG protein is localized in the nucleus of hFOB/ER cells, with the levels rapidly increasing after E2 treatment. The rapid E2-induced increase in TIEG expression is followed by an E2-induced inhibition of DNA synthesis in the hFOB/ER cells. Antiestrogens block not only the induction of TIEG mRNA levels but also the inhibition of cell proliferation. Lastly, hFOB cells, stably transfected with a TIEG expression vector, display markedly reduced DNA synthesis/cell proliferation, compared with nontransfected cells. These results support the finding that TIEG is an early responding regulatory gene for E2 in human osteoblast cells that inhibits DNA synthesis. It is speculated that TIEG may play a role in the signaling pathway for E2 in inhibiting cell proliferation.

Cell Division↗
PubMed1998

Effects of the circadian variation in serum cortisol on markers of bone turnover and calcium homeostasis in normal postmenopausal women.

Bone turnover has a circadian pattern, with bone resorption and, to a lesser extent, bone formation increasing at night. Serum cortisol also has a circadian pattern and is a potential candidate for mediating the circadian changes in bone turnover. Thus, we measured bone formation and resorption markers before (study A) and after (study B) elimination of the morning peak of cortisol. We also assessed effects of the circadian cortisol pattern on serum calcium, PTH, and urinary calcium excretion. Ten normal postmenopausal women, aged 63-75 yr (mean, 69 yr), were studied. Metyrapone was administered to block endogenous cortisol synthesis and either a variable (study A) or a constant (study B) infusion of cortisol was given to reproduce and then abolish the morning cortisol peak. Blood was sampled every 2 h for serum cortisol, ionized calcium, PTH, and bone formation markers [osteocalcin and carboxyl-terminal propeptide of type I collagen (PICP)], and timed 4-h urine samples were collected for measurement of calcium, phosphorus, sodium, potassium, and bone resorption markers (N-telopeptide of type I collagen and free deoxypyridinoline). During study A, serum osteocalcin had a circadian pattern, with a peak at 0400 h and a nadir at 1400 h. During study B, however, the afternoon nadir of serum osteocalcin was eliminated (P < 0.001 and P < 0.005 for the difference in the patterns of peak and nadir, respectively, on the 2 study days). In contrast, the circadian patterns of serum PICP and urinary N-telopeptide of type I collagen and free deoxypyridinoline were virtually identical during the two studies. Urinary calcium excretion declined after the cortisol peak, without differences between the 2 study days in phosphorus or sodium excretion or in serum PTH. We conclude that the circadian variation in serum cortisol is responsible for the circadian pattern of serum osteocalcin, but not that of PICP or bone resorption markers. The physiological variation in serum cortisol may also reduce urinary calcium excretion.

Aged↗
PubMed1998

A defect in renal calcium conservation may contribute to the pathogenesis of postmenopausal osteoporosis.

Although all postmenopausal women are estrogen deficient, women who have postmenopausal osteoporosis may have a defect, in addition to estrogen deficiency, that accounts for their higher rates of bone resorption and greater bone loss, relative to those who do not. To test the hypothesis that one defect is an impairment in renal calcium conservation, we measured renal calcium transport in 19 osteoporotic and 19 normal postmenopausal women, whose ages (median and 25th-75th percentile range) were 70 yr (range, 67-72) and 72 yr (range, 69-74), respectively. There was no difference between groups in values for serum ionized calcium and PTH concentrations or in renal filtered load of calcium. However, before PTH infusion, the osteoporotic women had lower (P = 0.0046) values for tubular reabsorption of calcium (TRCa) of 96.8% (range, 96.0-97.1) vs. 98.0% (range, 97.2-98.3) and higher (P = 0.0154) urinary calcium excretion of 0.194 mg/dL of glomerular filtrate (GF) (0.154-0.239) vs. 0.125 mg/dL of GF (0.103-0.173) than the normal women. After infusion of 200 U of synthetic PTH (synthetic 1-34 analog of human PTH), TRCa increased and calcium excretion decreased comparably in both groups, so that the differences between groups after intervention remained: for TRCa, 98.3% (97.7-98.6) vs. 98.9% (98.4-99.3; P = 0.0042); and for calcium excretion, 0.099 mg/dL of GF (0.080-0.138) vs. 0.066 mg/dL of GF, (0.045-0.097, P = 0.0180). In conclusion, postmenopausal women with osteoporosis have a PTH-independent defect in renal calcium conservation. This defect is of sufficient magnitude to contribute to the greater negative calcium balance in post-menopausal women with osteoporosis vs. their postmenopausal peers.

Absorption↗
PubMed1998

Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women: a key role for bioavailable estrogen.

Estrogen (E) deficiency associated with the menopause is the major cause of bone loss in aging women. However, men also lose significant amounts of bone with age, but they do not have the equivalent of menopause, and serum total testosterone (T) and E levels decline only marginally with age in men. Thus, it has been difficult to attribute bone loss in aging men to either T or E deficiency. Here, we show in a population-based, age-stratified sample of 346 men, aged 23-90 yr, that serum total T and E (estradiol plus estrone) levels decreased over the life span by 30% and 12%, respectively, but bioavailable (or nonsex hormone-binding globulin-bound) T and E levels decreased by 64% and 47%, respectively. In these men and in a parallel cohort of 304 women, aged 21-94 yr, serum PTH increased 84% and 64% over the life span, and urinary N-telopeptide of type I collagen (NTx) excretion, a bone resorption marker, increased 77% and 80% between age 50-85 yr in the men and women, respectively. By univariate analyses, serum bioavailable T and E levels correlated positively with bone mineral density (BMD) at the total body, spine, proximal femur, and distal radius and negatively with urinary NTx excretion in men and women. Urinary NTx excretion was also negatively associated with BMD in both sexes. By multivariate analyses, however, serum bioavailable E level was the consistent independent predictor of BMD in both men and postmenopausal women. Thus, bioavailable E levels decline significantly with age and are important predictors of BMD in men as well as women. These studies suggest that in contrast to traditional belief, age-related bone loss may be the result of E deficiency not just in postmenopausal women, but also in men.

Adult↗
PubMed1998

Treatment of established postmenopausal osteoporosis with raloxifene: a randomized trial.

Raloxifene is a selective estrogen receptor modulator that in experimental animals acts as an estrogen receptor antagonist in breast and endometrium but as an estrogen receptor agonist in the skeletal and cardiovascular systems. We conducted a 1-year prospective, randomized, double-blind trial in 143 postmenopausal osteoporotic women (mean +/- SD age, 68.4+/-5.0 years) with at least one prevalent vertebral fractures and low bone mineral density (BMD), comparing groups receiving raloxifene at 60 mg/day (RLX60) or 120 mg/day (RLX120) and a control group receiving supplements of 750 mg/day of calcium and 400 IU/day of vitamin D. There were no differences among groups in the occurrence of uterine bleeding, thrombophlebitis, breast abnormalities, or increased endometrial thickness (assessed by ultrasonography). As compared with controls, the changes in values over 1 year for RLX60 and RLX120, respectively, were significant for serum bone alkaline phosphatase (-14.9%, -8.87%), serum osteocalcin (-20.7%, -17.0%), and urinary C-telopeptide fragment of type I collagen/creatinine (-24.9%, -30.8%), markers of bone turnover; for serum total cholesterol (-7.0% for RLX60) and low density lipoprotein cholesterol (LDL) (-11.4% for RLX60) and for the LDL/HDL cholesterol ratio (-13.2%, -8.3%). BMD increased significantly in the total hip (1.66% for RLX60) and ultradistal radius (2.92%, 2.50%). There were nonsignificant trends toward increases over controls in BMD for lumbar spine, total body, and total hip (for RLX120). Using a >15% cutoff definition, raloxifene had no effect on incident fractures, but using a >30% cutoff, there was a dose-related reduction (p = 0.047). We conclude that raloxifene therapy is well tolerated, reduces serum lipids, and does not stimulate the uterus or breasts. It has beneficial effects on bone, although, under the conditions of this study, these appear to be of a smaller magnitude than have been reported with estrogen therapy.

Aged↗
PubMed1998

Bone density and fracture risk in men.

We evaluated different definitions of osteoporosis in a population-based sample of 348 men (age 22-90 years) compared with 351 women (age 21-93 years). Thirty-six men (10%) and 46 women (13%) had a history of osteoporotic fracture (hip, spine, or distal forearm due to moderate trauma at >/= age 35). In logistic regression analysis, osteoporotic fracture risk was associated with bone mineral density (BMD) at all sites (neck, trochanter, total hip, lumbar spine, and total wrist) in both genders (p < 0.001) except spinal BMD in men. After adjusting for age, total hip BMD was the strongest predictor of fracture risk in women (odds ratio [OR] per 1 SD decline, 2.4; 95% confidence interval [CI], 1.6-3.7), while wrist BMD was best in men (OR, 1.5; 95% CI, 1.1-2.0). Among men but not women, bone mineral apparent density (BMAD) was a better predictor of fracture than BMD (wrist BMAD OR, 1.7; 95% CI, 1.3-2.3). Hip BMD/BMAD decreased linearly from age 20 years onward in both genders, while spinal BMD/BMAD declined after age 40 in women but not in men. In both genders, total wrist BMD/BMAD decreased after age 50. By World Health Organization criteria, the age-adjusted prevalence of osteoporosis at the hip, spine, or wrist was 35% among women >/=50 years of age. A similar approach (BMD > 2.5 SD below the young male mean) produced an osteoporosis prevalence rate in men >/=50 years of age of 19%. Thus, bone density predicts fracture risk in men as it does in women, and the prevalence of osteoporosis in men, using sex-specific normal values, is substantial. These observations indicate a need for better prevention and treatment strategies for men.

Adult↗
PubMed1998

Long-term effects of calcium supplementation on serum parathyroid hormone level, bone turnover, and bone loss in elderly women.

We report a 4-year randomized, double-blind, placebo-controlled clinical trial in 236 normal postmenopausal women (mean age +/- SE, 66.3+/-0.2 years) who were randomized to a calcium (1600 mg/day as the citrate) or placebo group. The women were seen every 6 months; 177 completed the trial. Net percentage changes in each group are given relative to baseline. The differences in net percentage changes (calcium group minus placebo group) in medians were: for lumbar spine bone density, 2.0% (p < 0.001) at year 1 and 0.3% (not significant) at year 4; for proximal femur bone density, 1.3% (p = 0.003) at year 1 and 1.3% (p = 0.015) at year 4; and for total body bone mineral, 0.4% (p = 0.002) at year 1 and 0.9% (p = 0.017) at year 4. Similar differences at year 4 were: -18.9% (p = 0.002) for parathyroid hormone (PTH), -11.9% (p = 0.026) for serum osteocalcin, and -32.2% (p = 0.003) for urine free pyridinoline. We conclude that long-term administration of calcium supplements to elderly women partially reverses age-related increases in serum PTH level and bone resorption and decreases bone loss. However, the effects on bone loss were weaker than those reported for estrogen, bisphosphonates, or calcitonin therapy, indicating that calcium supplements alone cannot substitute for these in treating established osteoporosis. Nonetheless, because of their safety, high tolerance, and low expense, calcium supplements may be a useful preventive measure for elderly postmenopausal women whose bone mineral density values are normal for their age.

Aged↗
PubMed1998

Development and characterization of conditionally immortalized osteoblast precursor cell lines from human bone marrow stroma.

Although the differentiation of mature osteoblasts has been well studied, there is still a need for a convenient way to study preosteoblast differentiation. Our laboratory has recently described a method for isolating small numbers of authentic osteoblast precursor cells from human bone marrow (Rickard et al., J Bone Miner Res 11:312-324, 1996). Here we describe the conditional immortalization of these cells by retroviral transfection with the amphotrophic vector, pZipSV40tsa58, which encodes for a temperature-sensitive mutant form of the simian virus large T-antigen. At the permissive temperature of 34 degrees C, the cell lines proliferated, but differentiation was arrested, whereas at the restrictive temperature of 39.5 degrees C, proliferation was decreased and differentiation was induced. As assessed by semiquantitative reverse transcriptase PCR after 4 days of culture at 39.5 degrees C, the six cell lines expressed similar mRNA levels both constitutively and in response to dexamethasone (Dex) and 1alpha,25-dihydroxyvitamin D3 (1,25(OH2)D3) for osteoblast (alkaline phosphatase [ALP], type I collagen [Col I], osteocalcin [OC], and parathyroid hormone receptor [PTH-R] and adipocyte (lipoprotein lipase [LPL]) genes. In the presence of 10(-8) M Dex, gene expression for ALP, PTH-R, and LPL increased, but that for OC decreased. Stimulation with 10(-8) M 1,25(OH2)D3 increased gene expression for ALP, OC, and Col I. Changes in protein production for ALP, OC, and type I procollagen in response to Dex and 1,25(OH2)D3 were similar to changes in mRNA levels. When cultured at 39.5 degrees C with ascorbate and beta1-glycerolphosphate for 21 days, mineralization of matrix occurred, whereas culture with Dex plus 1,25(OH2)D3, or rabbit serum led to enhanced formation of cytoplasmic lipid droplets within 6 days. Thus, these cell lines are capable of bipotential differentiation and should serve as an excellent tool to study the molecular mechanisms that regulate and select for osteoblast and adipocyte differentiation in humans.

Adipocytes↗
PubMed1998

A unitary model for involutional osteoporosis: estrogen deficiency causes both type I and type II osteoporosis in postmenopausal women and contributes to bone loss in aging men.

We propose here a new unitary model for the pathophysiology of involutional osteoporosis that identifies estrogen (E) deficiency as the cause of both the early, accelerated and the late, slow phases of bone loss in postmenopausal women and as a contributing cause of the continuous phase of bone loss in aging men. The accelerated phase in women is most apparent during the first decade after menopause, involves disproportionate loss of cancellous bone, and is mediated mainly by loss of the direct restraining effects of E on bone cell function. The ensuing slow phase continues throughout life in women, involves proportionate losses of cancellous and cortical bone, and is associated with progressive secondary hyperparathyroidism. This phase is mediated mainly by loss of E action on extraskeletal calcium homeostasis which results in net calcium wasting and increases in the level of dietary calcium intake required to maintain bone balance. Because elderly men have low circulating levels of both bioavailable E and bioavailable testosterone (T) and because recent data suggest that E is at least as important as T in determining bone mass in aging men, E deficiency may also contribute substantially to the continuous bone loss of aging men. In both genders, E deficiency increases bone resorption and may also impair a compensatory increase in bone formation. For the most part, this unitary model is well supported by observational and experimental data and provides plausible explanations to traditional objections to a unitary hypothesis.

Aged↗
PubMed1998

Bone mass and muscle strength in female college athletes (runners and swimmers).

OBJECTIVE: To determine whether female college athletes had increased muscle strength and bone mass in comparison with age-matched nonathletic female subjects and, if so, whether participation in weight-bearing versus non-weight-bearing exercise made a difference. MATERIAL AND METHODS: We performed a comparative statistical analysis of the bone mineral density (BMD) of the total body, lumbar spine, and femoral neck, maximal oxygen uptake (VO2max), muscle strength, and level of physical activity in 21 runners, 22 swimmers, and 20 control subjects. The study participants were female college students, 18 to 24 years old, who had had more than 8 normal menstrual cycles during the past year. RESULTS: Statistical analyses showed significantly higher VO2max in the two athletic study groups than in the control subjects (P < 0.0001). No significant difference in BMD was noted among the three groups. Total body BMD (r = 0.30; P = 0.02) and femoral neck BMD (r = 0.39; P = 0.002) were positively correlated with weight-bearing activity but not with non-weight-bearing activity. VO2Max (an index of physical fitness) was positively correlated with femoral neck BMD (r = 0.33; P = 0.009) and trochanteric BMD (r = 0.29; P = 0.021). Shoulder muscle strength (determined by isokinetic dynamometry) was positively correlated with total body BMD (r = 0.34; P = 0.007) and lumbar spine BMD (r = 0.28; P = 0.028). Swimmers had higher muscle strength in the back and upper extremities than did runners and control subjects. Hip girdle muscle strength was not significantly different among the three groups. Total body BMD had a positive correlation with percentage of body fat and height. Lumbar spine BMD was higher in subjects who had previously used oral contraceptives. The athletes had a lower percentage of body fat, were less likely to have used oral contraceptives, and had fewer years of normal menses than did the control subjects. CONCLUSION: Our study shows that (1) total body BMD and femoral neck BMD were significantly higher in the study group that performed weight-bearing exercises than in control subjects, (2) swimming exercise had no effect on BMD, and (3) although swimming is not a bone-building exercise, it can significantly improve shoulder, back, and grip muscle strength.

Adult↗
PubMed1998

Effects of long-term transdermal administration of estradiol on serum lipids.

OBJECTIVE: To evaluate the effect of three different dosages of transdermally administered 17beta-estradiol on serum lipoproteins in women who had recently experienced surgical menopause. MATERIAL AND METHODS: We undertook a 2-year, randomized, double-blind, placebo-controlled study in which 126 subjects were recruited and stratified by age, and 93 patients completed the protocol. Serum lipoproteins were assessed before initiation of treatment and after 12 and 24 months of therapy with 0.025, 0.05, or 0.1 mg of estradiol daily. RESULTS: Total serum cholesterol and low-density lipoprotein cholesterol showed dose-dependent decreases that reached statistical significance after 2 years of treatment with transdermally administered estradiol. CONCLUSION: This study confirms that transdermally administered 17beta-estradiol has a modest beneficial effect on serum lipoproteins, with decreased levels of total cholesterol and low-density lipoprotein cholesterol.

Administration, Cutaneous↗
PubMed1997

Estrogen regulation of human osteoblastic cell proliferation and differentiation.

Estrogen (E2) has been shown to prevent bone loss among postmenopausal women. The molecular mechanism(s) by which this is accomplished is not clear. The discovery of E2 receptor (ER) in osteoblasts and osteoclasts has implicated these cells as direct targets for E2. Previous studies on the effects of E2 on osteoblastic cells in vitro or in organ culture present conflicting results, possibly due to heterogeneity in cell types, stage of differentiation, ER levels, and/or species differences. The effects of E2 on gene expression during various stages of human osteoblast cell differentiation has not been investigated extensively. In this study we employed a newly developed human fetal osteoblastic cell line (hFOB/ER9) that contains high levels of ER to examine the effects of E2 on osteoblast proliferation and differentiation. The basal levels and E2 effects on the expression of various extracellular matrix proteins were also characterized throughout different stages of differentiation. These stages include a proliferative/relatively undifferentiated stage (day 6), a matrix maturation stage (days 10-14), and a mineralization/calcified nodule stage (day 18). During the stage of rapid cell proliferation, E2 treatment of hFOB/ER9 cells resulted in a dose-dependent decrease in [3H]thymidine incorporation to a maximum of 72% compared to the vehicle control value. Treatment of hFOB/ER9 cells with 10(-9) M E2 for 48 h resulted in an increase in alkaline phosphatase (AP) activity throughout cell differentiation. The magnitude of AP induction varied from approximately 200-500%. In contrast, E2 decreased osteocalcin protein levels to a minimum of 54% compared to the vehicle control value. The steady state messenger RNA levels for AP increased and osteocalcin decreased after E2 treatment, similar to the responses observed at the protein level. At all stages, there was little or no effect of E2 on type I collagen protein levels or osteonectin steady state messenger RNA levels. The E2 responses on hFOB/ER9 cell matrix protein expression and cell proliferation were mediated through the ER, as cultures cotreated with a 100-fold molar excess of a type II anti-E2 (ICI 182,780) abrogated these effects. These results support the hypothesis that E2 does have an effect on osteoblastic differentiation by decreasing hFOB/ER9 cell proliferation and differentially regulating extracellular matrix expression.

Bone and Bones↗
PubMed1997

Effects of age and estrogen status on serum parathyroid hormone levels and biochemical markers of bone turnover in women: a population-based study.

Although estrogen deficiency is responsible for the increase in bone turnover in early postmenopausal women, age-related factors, such as the progressive increase in serum PTH levels, are believed to be responsible for the increase in bone turnover in elderly women. Whether estrogen deficiency continues to play a role, either directly or indirectly, in the pathogenesis of the increased bone turnover in elderly women remains unclear. Thus, we measured serum PTH, markers of bone turnover, and serum sex steroid levels in a population-based sample of 351 women (age range, 21-94 yr), which included 47 postmenopausal women who were receiving long term estrogen replacement therapy. Serum PTH increased as a function of age when the premenopausal women and the estrogen-deficient postmenopausal women were analyzed together (r = 0.35; P < 0.001). By contrast, this age-related increase in serum PTH was eliminated in the postmenopausal women receiving long term estrogen therapy, which also resulted in a similar suppression of markers of bone formation and resorption in both the early (< or = 20 yr) and late (> 20 yr) postmenopausal women. By multivariate analysis, serum 25-hydroxyvitamin D levels were highly predictive of serum PTH levels regardless of menopausal status, whereas serum estrone levels were predictive of markers of bone resorption in the postmenopausal women. We conclude that estrogen deficiency may be responsible not only for the increase in bone turnover in early postmenopausal women, but also indirectly for the secondary hyperparathyroidism and increase in bone turnover found in late postmenopausal women. Residual serum estrogen levels are important determinants of bone resorption in postmenopausal women.

Adult↗
PubMed1997

Relationship of bone turnover to bone density and fractures.

To assess the influence of bone turnover on bone density and fracture risk, we measured serum levels of osteocalcin (OC), bone alkaline phosphatase (BAP), and carboxy-terminal propeptide of type I procollagen (PICP), as well as 24-h urine levels of cross-linked N-telopeptides of type I collagen (NTx) and the free pyridinium cross-links, pyridinoline (Pyd) and deoxypyridinoline (Dpd), among 351 subjects recruited from an age-stratified random sample of Rochester, Minnesota women, PICP, NTx, and Dpd were negatively associated with age among the 138 premenopausal women. All of the biochemical markers were positively associated with age among the 213 postmenopausal women, and the prevalence of elevated turnover (> 1 standard deviation [SD] above the premenopausal mean) varied from 9% (PICP) to 42% (Pyd). After adjusting for age, most of the markers were negatively correlated with bone mineral density (BMD) of the hip, spine, or forearm as measured by dual-energy X-ray absorptiometry, and women with osteoporosis were more likely to have high bone turnover. A history of osteoporotic fractures of the hip, spine, or distal forearm was associated with reduced hip BMD and with elevated Pyd. After adjusting for lower BMD and increased bone resorption, reduced bone formation as assessed by OC was also associated with prior osteoporotic fractures. These data indicate that a substantial subset of elderly women has elevated bone turnover, which appears to adversely influence BMD and fracture risk. Combined biochemical and BMD screening may provide better prediction of future fracture risk than BMD alone.

Adult↗
PubMed1997

Role of estrogen deficiency in pathogenesis of secondary hyperparathyroidism and increased bone resorption in elderly women.

Whether the increased bone resorption and secondary hyperparathyroidism in elderly women is due to aging or to estrogen deficiency is unclear. To address this issue, we measured serum intact parathyroid hormone (PTH) and biochemical markers in serum and urine samples from 30 premenopausal women (32 +/- 0.5 years, mean age +/- SE), 30 estrogen-deficient postmenopausal women (74.2 +/- 0.6 years), and 30 elderly women (73.8 +/- 0.6 years) receiving long-term estrogen treatment. Because of the first and third groups were comparable in estrogen status but not in age, whereas the second and third groups were comparable in age but not in estrogen status, the independent effects of age and estrogen deficiency could be assessed quantitatively. Mean values were higher in the estrogen-deficient postmenopausal women than in the premenopausal women for serum PTH (by 33%, p < .01) and for bone resorption markers [by 50% p < .001) for urine cross-linked N-teleopeptide of type I collagen (NTx); 34% (p < .001) for urine pyridinoline (Pyd); and 36% (p < .001) for urine deoxypyridinoline (Dpd)]. However, mean values for serum PTH in the postmenopausal women receiving estrogen treatment did not differ from those in the premenopausal women, and mean values for bone resorption markers were not different (urine NTx and Pyd) or were lower [urine Dpd, by -12%, (p < .005)]. These findings suggest that late consequences of estrogen deficiency rather than age-related processes per se are the principal causes of the secondary hyperparathyroidism and increased bone resorption in elderly women.

Adult↗