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PubMed1991

Effect of calcitonin deficiency on bone density and bone turnover in totally thyroidectomized patients.

To investigate the influence of calcitonin deficiency on bone turnover and density we studied 25 premenopausal female and 12 male patients (age 23 to 49 years) who had undergone total thyroidectomy for differentiated thyroid cancer 1 to 15 years previously. Basal and calcium stimulated extractable calcitonin, representing the monomeric, biologically active form of the hormone, was lacking or markedly decreased in all patients. There was a relative increase of urine hydroxyproline excretion (an index of osteoclastic bone degradation) in relation to serum osteocalcin (an index of osteoblastic bone formation) indicating an imbalance of bone turnover with a tendency to increased degradation in all patients. Total and trabecular bone density, measured with quantitative computed tomography at the distal forearm were significantly decreased in the male and normal in the female patients, without a relation to the duration of the calcitonin deficiency. The study indicates that patients with calcitonin deficiency, suppressive thyroid hormone treatment, or both may have a higher risk of increased bone degradation and osteopenia. Whether the effect is more due to calcitonin deficiency or thyroid hormone therapy, cannot be concluded from this study design. The fact that only the male patients had a decreased bone density may be due to a lower parathyroid activity in our female patients and the greater thyroidectomy-induced decrement of monomeric calcitonin in our male patients compared with male controls.

Adult↗
PubMed1999

Effect of a short-term treatment with alendronate on bone density and bone markers in patients with central diabetes insipidus.

The aim of this open prospective randomized study was to evaluate the effect of a 6-month treatment with alendronate on the bone mineral density (BMD) at lumbar spine in patients with central diabetes insipidus. Eighteen patients with central diabetes insipidus and 18 sex- and age-matched healthy subjects entered this study. At study entry, all subjects underwent BMD assessment at the lumbar spine and measurement of serum osteocalcin (OC) and cross-linked N-telopeptides of type I collagen (Ntx). Thereafter, 9 of the 18 patients were randomized to receive treatment with alendronate at a dose of 10 mg, orally, once daily for 6 months (group 1), whereas the remaining 9 patients did not receive any treatment affecting bone status during this period (group 2). After 6 months, bone metabolism and bone density study were repeated in all patients. At baseline, lumbar BMD values (0.86+/-0.03 vs. 1.01+/-0.02 g/cm2; P<0.001) and serum OC levels (4.7+/-0.3 vs. 7.9+/-0.2 microg/L; P<0.001) were significantly lower, whereas urinary Ntx levels were significantly higher [72.0+/-1.9 vs. 64.6+/-1.7 nmol bone collagen equivalents (BCE)/nmol creatinine (Cr); P<0.01] in patients than in controls. After randomization, no difference in lumbar BMD, serum OC, or urinary Ntx was found between patients of group 1 and group 2. At the 6 month follow-up, no difference in serum OC levels was found compared to baseline evaluation in patients of both group 1 and group 2. By contrast, a significant decrease in urinary Ntx levels was found in patients of group 1 (70.3+/-3.0 vs. 75.4+/-2.1 nmol BCE/nmol Cr; P<0.05), but not in patients of group 2 (68.8+/-3.3 vs. 68.5+/-3.0 nmol BCE/nmol Cr; P = NS). A significant increase in lumbar BMD values was found in patients of group 1 (0.88+/-0.04 vs. 0.83+/-0.04 g/cm2; P<0.05), whereas a significant decrease in lumbar BMD values was found in patients of group 2 (0.86+/-0.05 vs. 0.89+/-0.05 g/cm2; P<0.05). Lumbar BMD increased 7.0+/-1.5% in patients of group 1 and decreased 4.2+/-1.8% in patients of group 2 (P<0.001). In conclusion, this study demonstrated that a 6-month treatment with alendronate in patients with central diabetes insipidus was effective in significantly improving BMD at the lumbar spine, which was significantly worsened in untreated patients. Therefore, alendronate treatment could be used in patients with central diabetes insipidus with documented osteopenia or osteoporosis.

Adolescent↗
PubMed1997

Comparison of alveolar bone loss, alveolar bone density and second metacarpal bone density, salivary and gingival crevicular fluid interleukin-6 concentrations in healthy premenopausal and postmenopausal women on estrogen therapy.

BACKGROUND: Osteoporosis is an age-related metabolic bone disease characterized by decreased mass and increased susceptibility to fracture. The literature suggests a relationship between oral bone loss and skeletal osteoporosis; however, most studies have produced conflicting results. The purpose of this study was to determine if a relationship exists among alveolar bone loss, alveolar bone density, second metacarpal density, salivary and gingival crevicular fluid interleukin 6 (IL-6), and IL-8 concentrations in premenopausal and postmenopausal healthy women receiving estrogen therapy. METHODS: Twenty-eight healthy women (aged 23-78) were evaluated for this study. A vertical bitewing and hand radiographs were taken, and the subjects were evaluated for the presence of active periodontitis. The bitewing and hand radiographs were digitized, and measurements were made from the cemento-enamel junction to the alveolar crest from both arches. Bone density was evaluated in the maxillary and mandibular alveolar process and at the mid-shaft of the second metacarpal. Percent cortical area and the moment of inertia measurements were also determined. Stimulated whole saliva was collected for a 5-min period using a cube of paraffin as a stimulant and was analyzed for total protein by a colorimetric reaction and IL-6 and IL-8 by ELISA. RESULTS: The results of the study showed that postmenopausal women on estrogen therapy had more alveolar bone loss, more missing teeth, and reduced alveolar and second metacarpal bone density than premenopausal women. In addition, postmenopausal women on estrogen therapy had higher salivary IL-6 concentrations than premenopausal women. Alveolar bone densities were also strongly correlated to second metacarpal densities. CONCLUSIONS: The results of the study suggest that changes in alveolar bone density and levels of bone resorptive cytokines in saliva may be secondary to changes in menopausal status. These changes may predispose loss of alveolar bone with resultant loss of teeth.

Adult↗
PubMed2004

[Effect of raloxifene hydrochloride on bone mineral density, bone metabolism and serum lipids in Chinese postmenopausal women with osteoporosis].

OBJECTIVE: To determine the effect of raloxifene hydrochloride (RLX) on the lumbar spine and total hip bone mineral density (BMD), bone metabolism and serum lipids in Chinese postmenopausal women with osteoporosis. METHODS: 204 Chinese postmenopausal women with osteoporosis from 3 hospitals in Beijing and Shanghai were randomly divided into 2 groups of 102 women: RLX group (RLX of the dosage of 60 mg/day was given for 12 months) and placebo group. In addition, 500 mg of elemental calcium and 200 units of vitamin D were given daily to all women. BMD, serum bone markers and lipids were measured before and after drug administration. The BMD of lumber spine and hip was measured by dual-energy X-ray absorptiometry (DEXA). Serum bone gamma-carboxyglutamic acid-containing protein (BGP) and C-teloppeptide were analyzed by one-step ELISA. Serum lipids were measured by enzymatic method. RESULTS: By the end of the 12-month study period, the lumbar spine BMD was increased by 3.3% +/- 4.8% in the RLX group and 1.0% +/- 4.9% in the placebo group (P < 0.001); the hip BMD was increased by 1.4% +/- 4.8%in the RLX group and decreased by 0.9% +/- 5.0% in the placebo group (P < 0.01). New vertebral fracture occurred in none of the subjects in the RLX group and in 5 subjects of the placebo group (P = 0.059). The serum BGP and CTX decreased by 41.7% and 61.5% respectively in the RLX group, both significantly more than those in the placebo group (10.6% and 35.6% respectively, both P < 0.001). Both the total cholesterol and low-density lipoprotein cholesterol were significantly lower in the RLX group than in the placebo group (both P < 0.001), however, there were no significant differences in high-density lipoprotein cholesterol and triglycerides between these two groups. One subject in the RLX group and 5 subjects in the placebo group discontinued the study due to adverse events. There were no differences in the number of subjects with hot flushes (3 in the RLX group and 1 in the placebo group) and the number of subjects with leg cramps (9 in the RLX group and 4 in the placebo group). No venous thromboembolic event was reported. CONCLUSION: RLX of the dosage of 60 mg/day for 12 months significantly increases the lumbar spine and total hip bone BMD, significantly decreases bone turnover and has favorable effects on serum lipids in Chinese postmenopausal women with osteoporosis.

1-Carboxyglutamic Acid↗
PubMed2006

Effects of risedronate on lumbar bone mineral density, bone resorption, and incidence of vertebral fracture in elderly male patients with leprosy.

There is no well-established treatment for osteoporosis in male patients with leprosy, because no clinical trials have examined the efficacy of treatment on bone mineral density (BMD) or fracture incidence in such patients. The purpose of the present study was to evaluate the therapeutic effect on oral administration of risedronate in male osteoporotic patients with leprosy. Twenty-three male patients with leprosy, 63-87 years of age, were randomly divided into two administration groups: R group (risedronate, 2.5 mg/day, daily) and P group (placebo, daily). The BMD of the lumbar spine (L2-L4) was measured by dual-energy X-ray absorptiometry, and urinary cross linked N-telopeptides of type I collagen (NTX) were assessed at baseline, 6 months, and 12 months after treatment. There were no significant differences in age, body mass index, BMD, or urinary NTX levels at baseline between the two groups. In the present study, oral administration of risedronate apparently prevented vertebral fractures by increasing lumbar BMD and caused a significant reduction in urinary NTX levels, while oral administration of placebo did not increase the lumbar BMD and prevent vertebral fractures due to osteoporosis. The above findings suggested that oral administration of risedronate contributed to the prevention of vertebral fractures by suppressing bone resorption and increasing in lumbar BMD in the elderly male patients with leprosy.

Aged↗
PubMed2002

Effect of discontinuation of estrogen, calcitriol, and the combination of both on bone density and bone markers.

In a 5-yr randomized prospective study we examined the treatment effect of estrogen replacement therapy/hormone replacement therapy (ERT/HRT), calcitriol, ERT/HRT and calcitriol, or placebo for 3 yr and the effect of discontinuation of therapy for 2 more yr on bone mineral density (BMD), calciotropic hormones, markers of bone remodeling, and calcium absorption in 489 elderly women. The treatment phase of the study was double-blinded. After discontinuing therapy for 2 yr, there was rapid bone loss in all 3 treatment groups, and most of the decrease in BMD occurred in the first year. In the ERT/HRT group, spine BMD increased 5.5% in yr 3, decreased 3.2% in yr 4, and decreased 0.7% in yr 5; femoral neck BMD increased 3.7% in yr 3, decreased 2.5% in yr 4, and decreased 0.4% in yr 5; total body BMD increased 2.1% in yr 3, decreased 1.4% in yr 4, and decreased 0.6% in yr 5. In the combination group, spine BMD increased 7.1% in yr 3, decreased 4.3% in yr 4, and decreased 0.3% in yr 5; femoral neck BMD increased 4.5% in yr 3, decreased 3.0% in yr 4, and decreased 0.01% in yr 5; total body BMD increased 2.2% in yr 3, decreased 1.5% in yr 4, and decreased 0.6% in yr 5. In the calcitriol group, spine BMD increased 1.8% in yr 3, decreased 1.8% in yr 4, and showed no change in yr 5; femoral neck BMD increased 0.2% in yr 3, decreased 0.2% in yr 4, and decreased 0.6% in yr 5; total body BMD decreased 0.4% in yr 3, decreased 0.6% in yr 4, and decreased 0.4% in yr 5. Compared with placebo, all treated groups at yr 5 had significantly higher total body BMD; only the combination group had significantly higher spine BMD (3.4%; P < 0.001) and total hip BMD (2.4%; P < 0.01.) compared with the placebo group. Compared with baseline, only spine BMD in the combination group was significantly higher (2.6%; P < 0.001) at yr 5. The increase in calcium absorption and the decrease in serum PTH levels in the calcitriol groups were reversed after discontinuation of treatment, and the decrease in bone markers was reversed in the hormone-treated groups. These results suggest that discontinuation of ERT/HRT and/or calcitriol therapy in elderly women leads to a decrease in much of the BMD gained on treatment; however, in the combination group there was a statistically significant residual effect on spine BMD.

Absorption↗
PubMed2005

Effects of exemestane administered for 2 years versus placebo on bone mineral density, bone biomarkers, and plasma lipids in patients with surgically resected early breast cancer.

PURPOSE: To evaluate potential detrimental effects of exemestane on bone and lipid metabolism. PATIENTS AND METHODS: Postmenopausal women with early breast cancer were randomly assigned to exemestane 25 mg daily or placebo for 2 years in a double-blind setting. Primary objective was to evaluate the effect of exemestane on bone mineral density. Secondary objectives were effects on bone biomarkers, plasma lipids, coagulation factors, and homocysteine. Planned size was 128 patients. RESULTS: One hundred forty-seven patients were enrolled. All patients completed their 24-month visit except for those discontinuing treatment at an earlier stage. The mean annual rate of bone mineral density loss was 2.17% v 1.84% in the lumbar spine (P = .568) and 2.72% v 1.48% in the femoral neck (P = .024) in the exemestane and placebo arm, respectively. The mean change in T-score after 2 years was -0.21 for exemestane and -0.11 on placebo in the hip, and -0.30 and -0.21, respectively, in the lumbar spine. Exemestane significantly increased serum level and urinary excretion of bone resorption, but also bone formation markers. Except for a modest reduction in high-density lipoprotein cholesterol (P < .001) and apolipoprotein A1 (P = .004), exemestane had no major effect on lipid profile, homocysteine levels, or coagulation parameters. CONCLUSION: Exemestane modestly enhanced bone loss from the femoral neck without significant influence on lumbar bone loss. Except for a 6% to 9% drop in plasma high-density lipoprotein cholesterol, no major effects on serum lipids, coagulation factors, or homocysteine were recorded. Bone mineral density should be assessed according to the US Preventive Services Task Force guidelines.

Aged↗
PubMed2000

Relationships between serum leptin level and regional bone mineral density, bone metabolic markers in healthy women.

BACKGROUND: Leptin might affect bone metabolism. This study was performed to investigate the relationship of leptin to bone metabolism in detail in premenopausal and postmenopausal healthy women. METHODS: The relationships between serum leptin level and bone mineral density of several regional sites of the body as well as whole body, along with bone metabolic markers, were examined in 47 premenopausal and 29 postmenopausal healthy women. RESULTS: Serum leptin level was weakly correlated with bone mineral density of pelvis (Pearson's correlation coefficient r=0.39, p<0.05) and left leg (r=0.41, p<0.01) in the premenopausal women, although the correlation decreased after adjustment for BMI. There was no significant relationship between serum leptin level and whole body bone mineral density both in the premenopausal and postmenopausal women. Serum leptin level was correlated with serum alkaline phosphatase (r=0.56, p<0.001) and urinary deoxypyridinoline/cr (r=-0.32, p<0.05) by Pearson's correlation test in the premenopausal women; the relationships were maintained even after adjustment for BMI (r=0.50 and -0.48, respectively). CONCLUSIONS: Leptin is not a key regulator of bone metabolism, although it may have some effects on bone metabolic markers and BMD regionally in premenopausal women.

Adult↗
PubMed2002

Effects of gender and age on the association of apolipoprotein E epsilon4 with bone mineral density, bone turnover and the risk of fractures in older people.

The aim of this study was to examine whether the presence of apolipoprotein E epsilon4 (ApoE epsilon4) is associated with a lower bone mineral density (BMD), lower quantitative ultrasound (QUS) measurements, higher bone turnover and fracture risk, and whether these relations are modified by gender and age. A total of 1406 elderly men and women (> or =65 years) of the Longitudinal Aging Study Amsterdam (LASA) participated in this study. In all participants, QUS measurements were assessed, as well as serum osteocalcin (OC) and urine deoxypyridinolin (DPD/Cr urine). Follow-up of fractures was done each three months. In a subsample ( n = 604), total body bone mineral content (BMC) and BMD of the hip and lumbar spine were measured. In addition, prevalent vertebral deformities were identified on radiographs. In women, the presence of ApoE epsilon4 was associated with significantly lower femoral neck BMD (g/cm(2); mean +/- SEM; epsilon4+, 0.64 +/- 0.01 vs. epsilon4-, 0.67 +/- 0.01; p = 0.04), lower trochanter BMD (g/cm(2); mean +/- SEM; epsilon4+, 0.58 +/- 0.01 vs. epsilon4-, 0.61 +/- 0.01; p = 0.01) and lower total body BMC (g; mean +/- SEM; epsilon4+, 1787 +/- 40.0 vs. epsilon4-, 1863 +/- 23.8; p = 0.04). Women with ApoE epsilon4 also had a higher risk of severe vertebral deformities (OR=2.78; 95%CI: 1.21-6.34). In men, the associations between ApoE status and both hip BMD and QUS depended on age. Only among the younger men (65-69 years) was the presence of ApoE epsilon4 associated with lower BMD values. Bone markers and fractures were not associated with ApoE epsilon4 in either women, or men. In conclusion, this large community-based study confirms the importance of ApoE epsilon4 as a possible genetic risk factor related to BMD and vertebral deformities and demonstrates that its effect is gender related, and depends on age in men only.

Aged↗
PubMed1995

Comparison between bone density and bone strength in glucocorticoid-treated aged ewes.

In order to assess if bone densitometry could be used as an indicator to evaluate bone fragility in short term studies performed on glucocorticoid-treated ewes, correlations between DXA measurements and biomechanical parameters obtained on the same bones were established in 27 aged ewes including sixteen animals treated with methylprednisolone 15 mg/day for 4 months and eleven untreated animals. DXA measurements were performed ex-vivo on HOLOGIC QDR-1000+ device. Biomechanical testings included a three-point bending test on the femur and a compression test on cylinders of cancellous bone excised from two lumbar vertebrae selected between L6 and L4. At the femoral site, bone mineral density was correlated with the bending stiffness (r = 0.65) and the ultimate bending strength (r = 0.64) whereas, at the vertebral site, biomechanical parameters failed to correlate with bone mineral density assessed by DXA. This apparent lack of correlation between vertebral bone mass and trabecular bone strength is mainly linked to anatomical characteristics of the ewe: in this species, the vertebral posterior arches, which consist mainly of cortical bone, are very large compared to the vertebral body and strongly influence the bone mineral density evaluated on the intact vertebra. This is not the case with other large animals, for instance non-human primates. In conclusion, DXA can give a good evaluation of bone strength for ewe femurs, but results must be interpreted carefully at the vertebral site due to the anatomical characteristics of this animal species.

Absorptiometry, Photon↗
PubMed2002

Vitamin D receptor gene allelic variants, bone density, and bone turnover in community-dwelling men.

The role of vitamin D receptor (VDR) gene polymorphisms in the determination of bone mass and bone turnover is controversial in women. The aim of the study was to determine whether VDR polymorphisms are associated with indices of bone mineral density (BMD) (by dual-energy X-ray absorptiometry and by ultrasound) and/or with bone turnover and muscle strength, factors related to both BMD and fracture risk. For this purpose, we investigated a cohort of community-dwelling men >70 years (n = 271) and a group of healthy control subjects between the ages of 20 and 50 years (n = 137). VDR TaqI, ApaI, and FokI genotypes were determined using enzymatic restriction digestion of polymerase chain reaction (PCR) fragments. In the elderly group, the lowest BMD value at the femoral neck and at the calcaneus was observed in subjects with the "At-At" haplotype genotype, with differences between extreme haplotype groups ("At-At" vs. noncarriers of the "At" allele) ranging from 5.8% to 34.3% (p < or = 0.05). Moreover, at the different subregions of the distal forearm and the tibia, the lowest BMD estimates were consistently associated in both elderly and younger men with the "At" haplotype allele, although this did not approach statistical significance. Elderly subjects with the "At-At" genotype had a significantly higher serum osteocalcin level. BMD was not significantly related to the FokI VDR polymorphism at any of the assessed skeletal sites, nor were any of the biochemical markers associated with the FokI VDR genotype. There were no differences between genotype groups for any of the indices of muscle strength. The present study indicates that the VDR genotype is associated with BMD in healthy community-dwelling elderly men and tends to be associated with biochemical markers, particularly of bone formation, in elderly men.

Adult↗
PubMed2005

Comparative effects of bicalutamide (Casodex) versus orchidectomy on bone mineral density, bone remodelling, and bone biomechanics in healthy rats.

INTRODUCTION: The aim of this work was to analyze the effects produced on bone mineral density (BMD) by the administration of bicalutamide and to compare them with those produced by orchidectomy. Bone formation rate (serum osteocalcin), bone resorption (serum carboxyterminal telopeptide of collagen I; CTX), and biomechanical properties of bone were also studied. METHODS: Thirty-eight male Wistar rats were used: (1) Sham group, rats sham operated at 16 weeks of age; (2) OQX group, rats orchidectomized at 16 weeks of age, and (3) Bic group, rats sham operated at 16 weeks of age and treated during 6 weeks with bicalutamide. The rats were sacrificed at 22 weeks of age, and the BMD in femur and lumbar spine was determined. Serum osteocalcin and serum CTX were also analyzed. Biomechanical parameters related to torsion assay were also studied. RESULTS: The OQX group showed a significant decrease in femoral BMD with respect to Sham rats, whereas bicalutamide treatment did not produce any significant change in BMD. Both Sham and Bic groups showed similar serum osteocalcin and CTX values, whereas OQX rats presented higher osteocalcin and CTX levels than the Sham group. The OQX group showed a significant decrease in femoral thickness. No significant differences were observed in the rest of the biomechanical parameters between groups. CONCLUSION: These results indicate that bicalutamide treatment, in spite of its anti-androgenic properties, does not affect bone remodelling nor BMD in male healthy rats, suggesting that this compound may function as a selective androgen receptor modulator for effects on bone remodelling in the osteoblasts.

Androgen Antagonists↗
PubMed1994

Modification of strain-specific femoral bone density by bone marrow-derived factors administered neonatally: a study on the spontaneously osteoporotic mouse, SAMP6.

SAMP6 is a recently developed strain of osteoporotic mice, and SAMP2 is a control for SAMP6 and has a higher peak bone mass. The bone mass of SAMP6 was increased until 2 months of age when a lysate of cells derived from the bone marrow of SAMP2 was injected at 1 or 4 days of age, but it was not increased when the lysate was injected at 21 days of age. No effect on bone mass was observed when lysates of other cells, bovine serum albumin or heat-inactivated lysate of bone marrow-derived cells of SAMP2, were injected. The ability to increase bone mass was not in the supernatant but in the pellet obtained by ultracentrifugation (105,000 g) of the lysate of bone marrow-derived cells of SAMP2. The lysate did not change the osteoclast surface but changed the appositional bone formation. In conclusion, the lysate of cells derived from the bone marrow of SAMP2 contains factors which can increase the bone mass of SAMP6, and these factors are present in the pellet obtained by ultracentrifugation.

Animals↗
PubMed2000

Effect of one year treatment with inhaled fluticasone propionate or beclomethasone dipropionate on bone density and bone metabolism: a randomised parallel group study in adult asthmatic subjects.

BACKGROUND: There is some concern that prolonged treatment with high doses of inhaled corticosteroids may have a detrimental effect on bone mass. The aim of this one year study was to investigate the effects of low and high doses of fluticasone propionate (FP) (400 microg/day and 750 microg/day) and beclomethasone dipropionate (BDP) (800 microg/day and 1500 microg/day) on bone mass and metabolism. METHODS: This was a multicentre, double blind, parallel group study involving 69 mild to moderate asthmatic subjects who were randomised to treatment as follows: 22 to FP400, 21 to BDP800, 13 to FP750, and 13 to BDP1500. Their mean age was 39 years, 67% were men, and all the women were premenopausal. RESULTS: The results of peripheral quantitative computed tomographic (pQCT) measurements (primary variable) showed that, compared with baseline values, there was no loss of trabecular or integral (cortical and trabecular) bone in the distal radius or tibia in any of the patients over the 12 month study period. No consistent pattern emerged from the analysis of changes from baseline in markers of bone formation and resorption after six and 12 months of treatment. CONCLUSION: The results of this study provide reassuring prospective one year data showing that inhaled corticosteroids, in the range of doses used, had no adverse effects on bone mass and metabolism in this group of asthmatic patients.

Administration, Inhalation↗