Bone Remodeling In Postmenopausal Women Research Articles

Effect of Padzahr Tablet on Biochemical Indices of Bone Remodeling in Postmenopausal Females with Osteopenia: A Randomized Double-Blind Placebo-Controlled Trial

Background: Osteoporosis is a complex disease that poses major global public health challenges. Many individuals with osteoporosis turn to complementary and alternative medicine (CAM) for prevention and management. Due to its mineral contents, Padzahr, a type of clay used in traditional Persian medicine, is believed to have bone-forming properties. This study examined the impact of Padzahr on bone remodeling in postmenopausal women with low bone density.Materials and Methods: In this randomized double-blind and placebo-controlled clinical trial, 48 postmenopausal women with osteopenia were included. The participants were divided into two groups, with 24 participants in each group. One group received Padzahr, and the other group received a placebo. The participants took their assigned treatment for 12 weeks. Blood samples were taken from participants at the study’s beginning and end to compare the two groups’ serum levels of bone remodeling biomarkers.Results: At the outset of the study, the two groups were similar and there were no significant differences in any of the measured variables. Additionally, the levels of bone turnover markers were not significantly different between the two groups at the start of the study (P>0.05). After 12 weeks of treatment, the results of the ANCOVA analysis showed no significant changes in the serum levels of bone turnover indices when comparing the Padzahr group to the placebo group (P>0.05). Conclusion: A clinical trial of 3 months of Padzahr treatment in postmenopausal women with osteopenia did not show significant changes in serum markers of bone turnover.

Role of food fortification with vitamin D and calcium in the bone remodeling process in postmenopausal women: a systematic review of randomized controlled trials

Foods containing vitamin D reduce the deficiency of this vitamin and improve bone turnover. To discuss effects of the intake of vitamin D-fortified foods in isolated form or associated with calcium on bone remodeling in postmenopausal women. PubMed, Lilacs, Scopus, and Bireme databases. OpenThesis and Google Scholar were searched as "grey literature". Medical subject headings or similar terms related to food fortified with vitamin D and bone in postmenopausal women were used. Information was collected on study methodology and characteristics of studied populations; dosage; the food matrix used as the fortification vehicle; duration of intervention; dietary intake; 25-hydroxyvitamin D [25(OH)D] levels; serum parathyroid hormone (PTH) concentrations; bone resorption and/or formation markers (ie, carboxy terminal cross-linked telopeptide of type I collagen [CTX], tartrate-resistant acid phosphatase isoform 5b [TRAP5b], and procollagen type 1 N-terminal propeptide [P1NP]); main results; and study limitations. Five randomized controlled trials involving postmenopausal women were included. The mean ages of participants ranged from 56.1 to 86.9 years. Daily consumption of soft plain cheese fortified with 2.5 µg of vitamin D3 and 302 mg of calcium for 4 weeks resulted in a mean increase of 0.8 ng/mL in 25(OH)D and 15.9 ng/mL in P1NP levels compared with baseline, and decreased CTX, TRAP5b, and PTH values. A similar intervention for 6 weeks, using fortified cheese, showed a reduction only in TRAP5b values (-0.64 U/L). Yogurt fortified with 10 µg of vitamin D3 and 800 mg of calcium did not change P1NP values after 8 weeks of intervention, but was associated with decreases of 0.0286 ng/mL and 1.06 U/L in PTH and TRAP5b, respectively. After 12 weeks of eating the fortified yogurt, 25(OH)D levels increased by a mean of 8.8 ng/mL and PTH levels decreased in by a mean of 0.0167 ng/mL. The interventions contributed toward the improvement of the bone resorption process but not to the bone formation process in postmenopausal women. CRD42019131976.

Temporal Change in Biomarkers of Bone Turnover Following Late Evening Ingestion of a Calcium-Fortified, Milk-Based Protein Matrix in Postmenopausal Women with Osteopenia.

The diurnal rhythm of bone remodeling suggests nocturnal dietary intervention to be most effective. This study investigated the effect of bedtime ingestion of a calcium-fortified, milk-derived protein matrix (MBPM) or maltodextrin (CON) on acute (0–4 h) blood and 24-h urinary change in biomarkers of bone remodeling in postmenopausal women with osteopenia. In CON, participants received 804 ± 52 mg calcium, 8.2 ± 3.2 µg vitamin D and 1.3 ± 0.2 g/kg BM protein per day. MBPM increased calcium intake to 1679 ± 196 mg, vitamin D to 9.2 ± 3.1 µg and protein to 1.6 ± 0.2 g/kg BM. Serum C-terminal cross-linked telopeptide of type I collagen (CTX) and procollagen type 1 amino-terminal propeptide (P1NP), and urinary N-telopeptide cross-links of type I collagen (NTX), pyridinoline (PYD) and deoxypyridinoline (DPD) was measured. Analyzed by AUC and compared to CON, a −32% lower CTX (p = 0.011, d = 0.83) and 24% (p = 0.52, d = 0.2) increase in P1NP was observed for MBPM. Mean total 24 h NTX excreted in MBPM was −10% (p = 0.035) lower than CON. Urinary PYD and DPD were unaffected by treatment. This study demonstrates the acute effects of bedtime ingestion of a calcium-fortified, milk-based protein matrix on bone remodeling.

Consumption of Vitamin D-and Calcium-Fortified Soft White Cheese Lowers the Biochemical Marker of Bone Resorption TRAP 5b in Postmenopausal Women at Moderate Risk of Osteoporosis Fracture ,

AbstractThe prevention of increased bone remodeling in postmenopausal women at low 10-y risk of osteoporotic fractures essentially relies on reinforcement of environmental factors known to positively influence bone health, among which nutrition plays an important role. In institutionalized women in their mid-eighties, we previously found that consumption of fortified soft plain cheese increased vitamin D, calcium, and protein intakes, reduced bone resorption biochemical markers, particularly the serum bone specific acid phosphatase tartrate resistant acid phosphatase, isoform 5b (TRAP 5b) that reflects osteoclast activity, and stimulated the serum bone anabolic factor insulin-like growth factor-I (IGF-I). Whether these effects occur in much younger women was tested in a prospective control study. Seventy-one healthy postmenopausal women aged 56.6 ± 3.9 y (mean ± SD) with low spontaneous supply of both Ca and vitamin D were randomized to consume daily (treated, n = 36) or not (controls, n = 35) two servings (2 × 100 g) of skimmed-milk, soft plain cheese for 6 wk. The vitamin D and Ca-fortified dairy product provided daily: 661 kJ, 2.5 μg vitamin D, 400 mg calcium, and 13.8 g protein. At the end of the intervention, the decrease in TRAP 5b and the increase in IGF-I were greater in the treated than in the control group (P < 0.02). The changes in serum carboxy terminal crosslinked telopeptide of type I collagen did not differ significantly between the two groups. In conclusion, like in elderly women, consumption by healthy postmenopausal women of a vitamin D and calcium-fortified dairy product that also increases the protein intake, reduces the serum concentration of the bone resorption biomarker TRAP 5b. This response, combined with the increase in serum IGF-I, is compatible with a nutrition-induced reduction in postmenopausal bone loss rate.

Bone remodeling in postmenopausal women who discontinued denosumab treatment: Off-treatment biopsy study

Denosumab is a fully human monoclonal antibody that neutralizes the activity of RANKL, leading to the inhibition of osteoclast maturation, bone-resorbing activity, and survival. Evaluation of trans-iliac crest bone biopsy specimens in the phase 3 pivotal fracture study with denosumab in postmenopausal women with osteoporosis showed evidence of reduced bone turnover at the tissue level in subjects receiving denosumab, and up to one-third of subjects did not have evidence of tetracycline labeling in trabecular or cortical bone. Discontinuation of denosumab therapy has demonstrated that the effects of denosumab are reversible, as assessed by biochemical markers of bone turnover (BTM) and BMD. The precise nature of changes that occur at the tissue level with denosumab discontinuation have not been explored. Fifteen subjects were enrolled in a cohort study to evaluate the effects of denosumab discontinuation at the tissue level. Subjects had discontinued osteoporosis treatment for a mean time of 25.1 months (range 21 to 29 months). Bone histomorphometry results were compared with results from placebo-treated women with osteoporosis in the denosumab phase 3 pivotal fracture bone biopsy substudy, and BTMs were compared with subjects' pretreatment values. The results of this study showed normal histology and bone remodeling similar to those observed in untreated postmenopausal women with osteoporosis. With treatment cessation, 100% of biopsy specimens had evidence of tetracycline labels. Biochemical markers were comparable to and highly correlated with pretreatment levels. These data confirm that the effects of denosumab on bone turnover at the tissue level are fully reversible.

Advanced imaging assessment of bone fragility in glucocorticoid-induced osteoporosis

Advanced bone imaging techniques provide structural information, beyond bone mineral density (BMD), and growing evidence indicates that BMD only partially explains bone strength and fracture resistance. Assessing glucocorticoid-induced osteoporosis (GIO) is important, especially the documentation of glucocorticoid (GC) impact on trabecular and cortical bone and on macro and microstructural features. Advanced methods for assessing macrostructure of bone include volumetric quantitative computed tomography (vQCT), high-resolution computed tomography (hrCT), and high-resolution magnetic resonance imaging (hrMRI). The methods for assessing bone microstructure include micro computed tomography (μCT) and micro magnetic resonance imaging (μMRI). Many advanced imaging techniques have been used in vitro and in vivo to examine structural effects of GIO in animals and in humans, and these applications are explored in this review. In human in vitro studies, investigators have used standard bone histomorphometry and μCT to compare trabecular microarchitecture and bone remodeling in postmenopausal women and in males with GIO, and have found that high-dose GC produces dramatic bone loss, accompanied by major reduction in trabecular connectivity and increases in trabecular perforations. In animal studies, investigators have used standard histomorphometry along with pQCT, vQCT, hrMRI or μCT to examine GIO in a variety of animal models including rats, minipigs and sheep. They generally have found excellent relationships between treatment-induced structural changes assessed by these advanced imaging techniques and changes in BMD and biomechanical properties. They also have examined various therapeutic interventions in animals and monitored their efficacy using quantitative imaging methods. In human in vivo studies, investigators have serially examined postmenopausal women and males with GIO in order to assess the extent of skeletal deterioration and to determine the best advanced measures of BMD and structure, with which to monitor disease activity and therapeutic response, and to predict fracture risk. They generally have found that bone density and structural measures obtained by pQCT, vQCT and hrMRI contributed substantially to understanding the skeletal effects of glucocorticoids and to predicting the risk of fracture in human GIO. These animal and human applications, illustrating advanced imaging in GIO, are still in early stages of development. However, as discussed in this review, the novelty and power of the imaging approaches are compelling, and their utility is promising.

Effect of dietary supplementation with collagen hydrolysates on bone metabolism of postmenopausal women with low mineral density

Collagen hydrolysates (CH), obtained by an enzymatic hydrolysis process of gelatins, have potential application as oral supplements. Objective: To evaluate the effects of diet supplementation with collagen hydrolysates on bone metabolism markers in postmenopausal women with low bone mineral density. Methods: A randomized double-blind clinical assay with postmenopausal women with osteopenia was planned. The volunteers ingested 10 g/day of CH or a placebo for a period of 24 weeks. The bone resorption markers (carboxyl-terminal collagen crosslinks—CTX) and bone formation markers (osteocalcin—OSCAL and bone-specific alkaline phosphatase—BAP) were determined at baseline and at 12 and 24 weeks of treatment. Results: The sample consisted of 35 placebo and 36 treated subjects (aged 57.3 ± 4.8 years and BMI of 27.4 ± 4.5 kg/m 2). BAP levels showed no significant changes over the time. CTX levels showed a significant increase during the 24 weeks of treatment from 0.40 to 0.48 ng/mL in CH group and 0.47 to 0.57 ng/mL in placebo group ( p < 0.0001). OSCAL levels also showed a increase during the 24 weeks from 24.8 to 29.0 ng/mL in CH group and 28.1 to 31.8 ng/mL in placebo group ( p < 0.001). A comparison of levels of bone markers between CH and placebo group demonstrated no differences. Analysis of variance revealed no significant effect of dietary supplementation with collagen hydrolysates on biochemical bone markers. Conclusions: CH consumption did not produce any effects on bone metabolism as measured by biochemical indices of bone remodeling in postmenopausal women. The majority of patients exhibited inadequate calcium intake, as well as excess body weight.

Effect of Black Cohosh on Biochemical Markers of Bone Remodeling in Postmenopausal Women

Effect of Black Cohosh on Biochemical Markers of Bone Remodeling in Postmenopausal Women

Differential Effects of Teriparatide and Alendronate on Bone Remodeling in Postmenopausal Women Assessed by Histomorphometric Parameters

An 18-month randomized double-blind study was conducted in postmenopausal women with osteoporosis to compare the effects of once-daily teriparatide 20 microg with alendronate 10 mg on bone histomorphometry. Biopsies were obtained from 42 patients. Indices of bone formation were significantly higher after 6 or 18 months of teriparatide compared with alendronate treatment. Alendronate and teriparatide increased BMD, assessed by DXA, by different mechanisms of action, supported by changes in biochemical markers of bone turnover. The purpose of this cross-sectional study was to explore the differential effects of these two osteoporosis treatments at the bone tissue level by examining bone histomorphometric parameters of bone turnover after either 6 or 18 months of treatment. Patients were a cohort from a randomized parallel double-blind study conducted to compare the effects of once-daily teriparatide 20 microg and alendronate 10 mg in postmenopausal women with osteoporosis. Transiliac crest bone biopsies were obtained after tetracycline double labeling from 42 patients treated for 6 months (n = 23) or 18 months (n = 14); 5 additional patients were biopsied from contralateral sides at 6 and 18 months. Biopsy specimens adequate for quantitative analysis were analyzed by 2D histomorphometry from 17 patients at 6 months (teriparatide, n = 8; alendronate, n = 9) and 15 patients at 18 months (teriparatide, n = 8; alendronate, n = 7). Data were analyzed by two-sample tests. Histomorphometric indices of bone formation were significantly and markedly greater in the teriparatide group than in the alendronate group at 6 and 18 months, whereas indices of bone resorption were only significantly greater in the teriparatide group than in the alendronate group at 6 months. Bone formation and activation frequency were significantly lower at 18 months compared with 6 months in the teriparatide group, returning to levels comparable with untreated postmenopausal women. In the teriparatide group, the peak in histomorphometric bone formation indices coincided with peak levels for N-terminal propeptide of type I collagen, a biochemical marker of bone formation. The degree of mineralization was lower at 18 months than at 6 months with treatment in both groups but was not different between groups. These results confirm the opposite mechanisms of action of teriparatide and alendronate on bone remodeling and confirm the bone formation effect of teriparatide.

Consumption of a high calcium mineral water lowers biochemical indices of bone remodeling in postmenopausal women with low calcium intake

Many postmenopausal women have a calcium intake far below the recommended amount and, in addition to attempting to improve their diet, need a calcium supplement. The aim of the study was to assess the effects of the consumption of a high calcium mineral water (HCaMW) on biochemical indices of bone remodeling in postmenopausal women with low Ca intake. A 6-month randomized double-blind placebo-controlled trial was designed to assess the effects of a daily consumption of 1 liter of a HCaMW (596 mg Ca/l) on serum parathyroid hormone (PTH) and biochemical markers of bone remodeling in postmenopausal women with a dietary Ca intake lower than 700 mg/day. The placebo group drank 1 liter of a mineral water with a low calcium content (10 mg/l). One hundred eighty healthy women were recruited (mean age: 70.1+/-4.0 years); 152 completed the 6-month trial. The changes from baseline of biochemical indices after 6 months consisted of a significant 14.1% decrease of serum PTH, osteocalcin (-8.6%), bone alkaline phosphatase (-11.5%), serum (-16.3%) and urine (-13.0%) type-1 collagen C-telopeptide in the HCaMW group compared to the placebo group, where all biochemical indices increased after 6 months. The additive effect of a small vitamin D supplement (400 iu/day) was also evaluated. In women receiving vitamin D in addition to HCaMW, the decrease in bone indices was not found to be greater than in women drinking only the HCaMW. A daily supplement of 596 mg of Ca through the consumption of 1 l of HCaMW was able to lower serum PTH and the indices of bone turnover in postmenopausal women with a low Ca intake. This could contribute to the repair of calcium deficiency and to the reduction of age-related bone loss in this population.

Additive Effects of Raloxifene and Alendronate on Bone Density and Biochemical Markers of Bone Remodeling in Postmenopausal Women with Osteoporosis

More skeletal benefit has reportedly been achieved using two antiresorptive treatments in combination, presumably because these treatments have different mechanisms of action. Bisphosphonates such as alendronate (ALN) bind to hydroxyapatite and inhibit bone resorption by reducing osteoclast numbers and activity. The selective estrogen receptor modulators, including raloxifene (RLX), act in a tissue-specific manner by binding to estrogen receptors and then to target genes, modifying gene expression. This study examined the results of these two agents, alone and in combination, compared with placebo. Lumbar spine and femoral neck bone mineral density (BMD) were estimated, and biochemical markers of bone metabolism determined in 331 postmenopausal women with established osteoporosis. Using a randomized double-blind design, the participants were given placebo, RLX in a dose of 60 mg daily, 10 mg daily of ALN, or both active treatments in combination for 12 months. The study was completed by 274 women, with no differences in baseline characteristics among the treatment groups. After 12 months, BMD in both the lumbar spine and femoral neck was significantly greater than at baseline in all treatment groups (Fig. 1), and also significantly more than in placebo recipients. Spinal BMD increased significantly more in patients given ALN alone than in the RLX group. Femoral BMD improved more with combination treatment than in patients given RLX only. All biochemical markers of bone turnover decreased from baseline after 12 months in the study, and all differed from placebo values (Fig. 2). The declines in bone marker levels were comparable in the ALN and combination treatment groups, but were more marked in both of these groups than with RLX alone. Additional analysis suggested that RLX and ALN act independently on BMD, and that the effects are additive. There were no substantial differences in rates of adverse effects among the group, and withdrawal rates did not differ significantly. A combination of ALN and RLX increased BMD more than either agent alone in this trial, conducted in postmenopausal women with osteoporosis. The effects of combined treatment on the risk of fracture remain unknown, as is the long-term clinical safety of combination therapy.

Additive Effects of Raloxifene and Alendronate on Bone Density and Biochemical Markers of Bone Remodeling in Postmenopausal Women with Osteoporosis

Additive Effects of Raloxifene and Alendronate on Bone Density and Biochemical Markers of Bone Remodeling in Postmenopausal Women with Osteoporosis

Effects of lower doses of conjugated equine estrogens (CEE) and medroxyprogesterone acetate (MPA) on bone.

Objective: To evaluate the effects of variable doses of CEE, either alone or with one of two daily doses of MPA, on bone mineral density (BMD) and markers of bone remodeling. Design: 749 healthy postmenopausal women who participated in the Osteoporosis and Metabolic substudy of the double-blind, placebo-controlled Women’s Health, Osteoporosis, Progestin, Estrogen (Women’s HOPE) study were randomized to receive CEE 0.625 mg/day, CEE 0.625/MPA 2.5 mg/day, CEE 0.45 mg/day, CEE 0.45/MPA 2.5 mg/day, CEE 0.45/MPA 1.5 mg/day, CEE 0.3 mg/day, CEE 0.3/MPA 1.5 mg/day, or placebo. All women received calcium carbonate (600 mg elemental calcium daily). Women were between 1 and 4 years post-menopause at enrollment. Materials/Methods: BMD (lumbar spine, femoral neck, trochanter, and total body; Lunar DPX-L, Lunar Corp., Madison, WI) and bone remodeling markers (serum osteocalcin [OC] and urine N-telopeptide [NTX]) were measured at baseline and every 6 months for 2 years. Replicate BMD measurements were obtained at baseline and study completion. A single technician following a standard protocol performed all BMD scans. To examine the effects of each dose, data were analyzed using a modified efficacy-evaluable population that excluded patients who were >80% compliant with study medication, used non-study medications that affected calcium or skeletal homeostasis, or did not have at least 1 baseline scan and 2 on-treatment scans. Scans performed >60 days after stopping study medication were not included in analyses. Statistical significance was set a priori at P<.05. Results: By study completion, placebo-treated patients had lost BMD at spine, femoral neck, and total body while trochanter BMD remained stable (loss ∼2%–3% over 2 years). All doses of CEE and CEE/MPA produced significant increases in BMD at all sites relative to placebo, with differences ranging from 4%–6.4% (spine) to 2%–2.6% (total body), with hip differences intermediate. All doses increased BMD from baseline at all sites, except CEE 0.3 mg, which just failed to reach statistical significance. There was a dose-response relationship across all doses in the spine, confirmed by a responder analysis that indicated that 87% of individuals increased BMD in the spine at 0.625 CEE, but only 63% at 0.3 mg. Total body BMD also showed a dose-response relationship. As expected, CEE and CEE/MPA reduced both OC and NTX by 26%–38% and 36%–55%, respectively, with little evidence of a dose-response. Conclusions: Lower doses of CEE, alone or in combination with either 2.5 or 1.5 mg/day of MPA, preserve BMD and reduce markers of bone remodeling in postmenopausal women. The findings also confirm that calcium alone, supplemented at 600 mg/day, does not prevent bone loss in the early, postmenopausal years. Supported By: Wyeth-Ayerst Research.

Efecto de dosis bajas de calcitonina sobre la remodelación ósea en mujeres postmenopáusicas con alto recambio

Calcitonin is specially indicated for the treatment of osteoporosis in women that cannot receive estrogen replacement therapy or that have a high bone turnover rate. To study the effects of low intranasal calcitonin doses on bone remodeling in postmenopausal women with a high bone turnover. Forty one healthy women aged 56 +/- 6 years old, with a mean lapse after menopause of 7.6 +/- 6.5 years and with a high bone turnover rate, evidenced by an urinary hydroxyproline (mg/dl)/creatinine (g/dl) ratio of 52.4 +/- 7.2, were studied. They were randomly assigned to receive 100 or 50 U/calcitonin thrice a week during 3 months or to a control group that received placebo. All received 500 mg/day calcium carbonate. Urinary hydroxyproline/creatinine ratio was measured a 0, 15, 30, 60 and 90 days. Plasma bone fraction of alkanine phosphatases was measured at 0, 30 and 90 days. Initial urinary hydroxyproline/creatinine ratio and plasma bone fraction of alkanine phosphatases were similar in all study groups and there was no change in these parameters during the study period. Intranasal calcitonin in doses of 100 U thrice a week or less, does not modify accelerated bone turnover in postmenopausal women.

Aromatase expression and activity in the human leukaemic cell line FLG 29.1

The recent observation that estrogen synthesis occurs in osteoblast-like cells has suggested the aromatase activity as a possible local modulator of bone remodeling in post-menopausal women. To provide further insights into the androstenedione conversion to estrogen in bone-derived cells, we examined the human leukaemic cell line FLG 29.1, which is induced to differentiate toward the osteoclastic phenotype by TPA and TGF- β1. Southern blot of RT-PCR products with a 32P-labeled cDNA probe for the human aromatase demonstrated that FLG 29.1 cells express aromatase mRNA. The enzyme activity, determined by measuring [ 3H]H 2O release from [ 3H]androstenedione, obeyed Michaelis–Menten kinetic with apparent Km and V max values ranging from 5 to 10 nM and from 200 to 400 fmol/mg protein/6 h. Gene expression, enzyme activity and protein immunoreactivity, evaluated by immunocytochemistry, were stimulated in a time-dependent fashion by 5% charcoal-stripped FCS and by either 1–100 nM TPA or 0.01–0.5 ng/ml TGF- β1, with maximal responses after 2–3 h exposure. After 24 h incubation of FLG 29.1 cells in the absence of these stimuli the aromatase mRNA and the protein were barely detectable. These findings demonstrate that cells of the osteoclastic lineage synthesize estrogen in vitro and that local cytokines, such as TGF- β1, are able to induce androstenedione conversion.

The effects of long-term hormone replacement therapy on bone remodeling in postmenopausal women

Hormone replacement therapy prevents menopausal bone loss and reduces the risk of fragility fracture, but its effects on bone remodeling have not been clearly established. We studied the effects of long-term hormone replacement therapy on bone turnover and remodeling balance in 22 post-menopausal women with osteopenia or osteoporosis. Iliac crest biopsies were obtained before and after treatment (mean 23.5 months) after double tetracycline labeling and subjected to histomorphometric analysis. Post-treatment biopsies showed a significant reduction in bone formation rate at tissue level and activation frequency ( p = 0.002 and 0.01, respectively). There was also a reduction in mineral appositional rate ( p = 0.0002) and osteoid seam width ( p = 0.01), but no significant change in mineralization lag time or osteoid maturation period. Wall width showed a significant decrease after treatment ( p = 0.03) and there was a consistent trend toward a reduction in resorption cavity dimensions with a statistically significant decrease in the resorption cavity length ( p = 0.03). These results confirm the previously reported reduction in bone turnover in postmenopausal women treated with hormone replacement therapy. Post-treatment biopsies also showed a reduction in resorption cavity size and a decrease in wall width, the latter possibly reflecting a compensatory change in response to the reduction in erosion depth. Our data do not provide any evidence that conventional hormone replacement therapy has anabolic effects at the level of the bone remodeling unit and indicate that its beneficial skeletal effects result from suppression of bone turnover and a reduction in the size of resorption cavities.

Interactions of growth hormone and parathyroid hormone in renal phosphate, calcium, and calcitriol metabolism and bone remodeling in postmenopausal women

The mechanisms underlying the effects of recombinant human growth hormone (rhGH) on vitamin D, mineral, and bone metabolism are not known. We examined whether these effects are mediated by parathyroid hormone (PTH) by measuring renal phosphorus (P) and calcium (Ca) handling, serum calcitriol, and markers of bone turnover for 24 h before and 72 h after an infusion of hPTH(1-34) in eight healthy postmenopausal women at baseline and following short-term (1 week) and sustained (5 weeks) rhGH treatment. On short-term rhGH, serum phosphorus and basal TmP/GFR were unaffected, but the fall in TmP/GFR after hPTH infusion was exaggerated (integrated response: -99.2 +/- 22.3 versus -144.1 +/- 15.0 minute-mg/dl, P = 0.0021). Basal calcitriol levels rose from 115 +/- 17 to 163 +/- 16 pM (P = 0.0002), but the increase in calcitriol following hPTH infusion was unaffected by short-term rhGH. The basal Ca excretion index (CEI) rose from 0.054 +/- 0.005 to 0.073 +/- 0.007 mM (P = 0.0095), but markers of bone turnover were unaffected. With sustained rhGH treatment, serum P (1.47 +/- 0.05 mM), basal TmP/GFR (4.29 +/- 0.24 mg/dl), and basal CEI (0.067 +/- 0.005 mM) were elevated compared with control values, and the PTH-induced lowering of TmP/GFR was again enhanced (-158.7 +/- 22.8 minute-mg/dl, P = 0.0021). Basal calcitriol concentrations returned to control levels (108 +/- 10 pM), but the calcitriol response to hPTH remained unchanged. Markers of bone remodeling were elevated with sustained rhGH treatment.(ABSTRACT TRUNCATED AT 250 WORDS)