Bone mineral density in young women with long-standing amenorrhea: limited effect of hormone replacement therapy with ethinylestradiol and desogestrel

To assess bone mineral density (BMD) at different skeletal sites in women with hypothalamic or ovarian amenorrhea and the effect of estrogen-gestagen substitution on BMD we compared BMD of 21 amenorrheic patients with hypothalamic or ovarian amenorrhea with that of a control population of 123 healthy women. All amenorrheic patients were recruited from the outpatient clinic of the Division of Gynecological Endocrinology at the University of Berne, a public University Hospital. One hundred and twenty-three healthy, regularly menstruating women recruited in the Berne area served as a control group. BMD was measured using dual-energy X-ray absorptiometry (DXA). At each site where it was measured, mean BMD was lower in the amenorrheic group than in the control group. Compared with the control group, average BMD in the amenorrheic group was 85% at lumbar spine (p < 0.0001), 92% at femoral neck (p < 0.02), 90% at Ward's triangle (p < 0.03), 92% at tibial diaphysis (p < 0.0001) and 92% at tibial epiphysis (p < 0.03). Fifteen amenorrheic women received estrogen-gestagen replacement therapy (0.03 mg ethinylestradiol and 0.15 mg desogestrel daily for 21 days per month), bone densitometry being repeated within 12-24 months. An annual increase in BMD of 0.2% to 2.9% was noted at all measured sites, the level of significance being reached at the lumbar spine (p < 0.0012) and Ward's triangle (p < 0.033). In conclusion BMD is lower in amenorrheic young women than in a population of normally menstruating, age-matched women in both mainly trabecular (lumbar spine, Ward's triangle, tibial epiphysis) and mainly cortical bone (femoral neck, tibial diaphysis).(ABSTRACT TRUNCATED AT 250 WORDS)

Cortical and trabecular bone mineral density in transsexuals after long-term cross-sex hormonal treatment: a cross-sectional study

The aim of this study was to explore the effect of long-term cross-sex hormonal treatment on cortical and trabecular bone mineral density and main biochemical parameters of bone metabolism in transsexuals. Twenty-four male-to-female (M-F) transsexuals and 15 female-to-male (F-M) transsexuals treated with either an antiandrogen in combination with an estrogen or parenteral testosterone were included in this cross-sectional study. BMD was measured by DXA at distal tibial diaphysis (TDIA) and epiphysis (TEPI), lumbar spine (LS), total hip (HIP) and subregions, and whole body (WB) and Z-scores determined for both the genetic and the phenotypic gender. Biochemical parameters of bone turnover, insulin-like growth factor-1 (IGF-1) and sex hormone levels were measured in all patients. M-F transsexuals were significantly older, taller and heavier than F-M transsexuals. They were treated by cross-sex hormones during a median of 12.5 years before inclusion. As compared with female age-matched controls, they showed a significantly higher median Z-score at TDIA and WB (1.7+/-1.0 and 1.8+/-1.1, P < 0.01) only. Based on the WHO definition, five (who did not comply with cross-sex hormone therapy) had osteoporosis. F-M transsexuals were treated by cross-sex hormones during a median of 7.6 years. They had significantly higher median Z-scores at TEPI, TDIA and WB compared with female age-matched controls (+0.9+/-0.2 SD, +1.0+/-0.4 SD and +1.4+/-0.3 SD, respectively, P < 0.0001 for all) and reached normal male levels except at TEPI. They had significantly higher testosterone and IGF-1 levels (p < 0.001) than M-F transsexuals. We conclude that in M-F transsexuals, BMD is preserved over a median of 12.5 years under antiandrogen and estrogen combination therapy, while in F-M transsexuals BMD is preserved or, at sites rich in cortical bone, is increased to normal male levels under a median of 7.6 years of androgen treatment in this cross sectional study. IGF-1 could play a role in the mediation of the effect of androgens on bone in F-M transsexuals.

Effects of nasal calcitonin on bone mineral density following parathyroidectomy in patients with primary hyperparathyroidism

To investigate whether nasal salmon calcitonin (CT; 200 U/day) given in addition to calcium helps to restore the bone mass after parathyroidectomy (PTX) in patients with primary hyperparathyroidism (PHPT).

Changes in bone mineral density over 18 months following kidney transplantation: the respective roles of prednisone and parathyroid hormone

Prednisone is a major factor of bone loss after kidney transplantation. The role of hyperparathyroidism and immunosuppressors is less clear.

Effect of disodium monofluorophosphate, calcium and vitamin D supplementation on bone mineral density in patients chronically treated with glucocorticosteroids: a prospective, randomized, double-blind study

To study the effect of fluoride on bone mineral density (BMD) in patients treated chronically with glucocorticosteroids, 15 subjects (renal grafted, n = 12; skin disease, n = 1; broncho pulmonary disorder, n = 1; Crohn's disease, n = 1) were prospectively studied in a double-blinded manner and randomly allocated either to group 1 (n = 8) receiving 13.2 mg/day fluoride given as disodium monofluorophosphate (MFP) supplemented with calcium (1,000 mg/day) and 25-hydroxyvitamin D (calcifediol) (50 micrograms/day), or to group 2 (n = 7) receiving Cas+ calcifediol alone. An additional group of 14 renal transplant patients treated chronically with glucocorticosteroids but exempt of specific therapeutic intervention for bone disease was set up as historical controls. BMD was measured by dual-energy X-ray absorptiometry (DXA, Hologic QDR 1000) performed at months 0, 6 and 12 for groups 1 and 2 (lumbar spine, total upper femur, diaphysis and epiphysis of distal tibia), or 11-31 months apart with calculation of linear yearly changes for the historical cohort. Lumbar BMD tended to rise in groups 1 and 2, and to fall in group 3, the change reaching statistical significance (p < 0.05) in group 1, thus leading to a significant difference between groups 1 and 3 (p < 0.05). At upper femur, tibial diaphysis and tibial epiphysis, no significant change in BMD occurred in any of the groups. In conclusion, lumbar BMD rises more after a mild dosis of fluoride given as MFP and combined to calcium and calcifediol than on Ca+ calcifediol alone, without changes in BMD at the upper femur or distal tibia.

Bone mineral density at distal tibia using dual-energy X-ray absorptiometry in normal women and in patients with vertebral osteoporosis or primary hyperparathyroidism

To assess the effect of age and disease on mineral distribution at the distal third of the tibia, bone mineral content (BMC) and bone mineral density (BMD) were measured at lumbar spine (spine), femoral neck (neck), and diaphysis (Dia) and distal epiphysis (Epi) of the tibia in 89 healthy control women of different age groups (20-29, n = 12; 30-39, n = 11; 40-44, n = 12; 45-49, n = 12; 50-54, n = 12; 55-59, n = 10; 60-69, n = 11; 70-79, n = 9), in 25 women with untreated vertebral osteoporosis (VOP), and in 19 women with primary hyperparathyroidism (PHPT) using dual-energy x-ray absorptiometry (DXA; Hologic QDR 1000 and standard spine software). A soft tissue simulator was used to compensate for heterogeneity of soft tissue thickness around the leg. Tibia was scanned over a length of 130 mm from the ankle joint, fibula being excluded from analysis. For BMC and BMD, 10 sections 13 mm each were analyzed separately and then pooled to define the epiphysis (Epi 13-52 mm) and diaphysis area (Dia 91-130 mm). Precision after repositioning was 1.9 and 2.1% for Epi and Dia, respectively. In the control group, at any site there was no significant difference between age groups 20-29 and 30-39, which thus were pooled to define the peak bone mass (PBM).(ABSTRACT TRUNCATED AT 250 WORDS)

Dual-energy X-ray absorptiometry for measuring total bone mineral content in the rat: study of accuracy and precision

Sequential studies of osteopenic bone disease in small animals require the availability of non-invasive, accurate and precise methods to assess bone mineral content (BMC) and bone mineral density (BMD). Dual-energy X-ray absorptiometry (DXA), which is currently used in humans for this purpose, can also be applied to small animals by means of adapted software. Precision and accuracy of DXA was evaluated in 10 rats weighing 50-265 g. The rats were anesthetized with a mixture of ketamine-xylazine administrated intraperitoneally. Each rat was scanned six times consecutively in the antero-posterior incidence after repositioning using the rat whole-body software for determination of whole-body BMC and BMD (Hologic QDR 1000, software version 5.52). Scan duration was 10-20 min depending on rat size. After the last measurement, rats were sacrificed and soft tissues were removed by dermestid beetles. Skeletons were then scanned in vitro (ultra high resolution software, version 4.47). Bones were subsequently ashed and dissolved in hydrochloric acid and total body calcium directly assayed by atomic absorption spectrophotometry (TBCa[chem]). Total body calcium was also calculated from the DXA whole-body in vivo measurement (TBCa[DXA]) and from the ultra high resolution measurement (TBCa[UH]) under the assumption that calcium accounts for 40.5% of the BMC expressed as hydroxyapatite. Precision error for whole-body BMC and BMD (mean +/- S.D.) was 1.3% and 1.5%, respectively. Simple regression analysis between TBCa[DXA] or TBCa[UH] and TBCa[chem] revealed tight correlations (n = 0.991 and 0.996, respectively), with slopes and intercepts which were significantly different from 1 and 0, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Gene array of primary human osteoblasts exposed to enamel matrix derivative in combination with a natural bone mineral

OBJECTIVES The application of an enamel matrix derivative (EMD) for regenerative periodontal surgery has been shown to promote formation of new cementum, periodontal ligament, and alveolar bone. In intrabony defects with a complicated anatomy, the combination of EMD with various bone grafting materials has resulted in additional clinical improvements, but the initial cellular response of osteoblasts coming in contact with these particles have not yet been fully elucidated. The objective of the present study was to evaluate the in vitro effects of EMD combined with a natural bone mineral (NBM) on a wide variety of genes, cytokines, and transcription factors and extracellular matrix proteins on primary human osteoblasts. MATERIAL AND METHODS Primary human osteoblasts were seeded on NBM particles pre-coated with versus without EMD and analyzed for gene differences using a human osteogenesis gene super-array (Applied Biosystems). Osteoblast-related genes include those transcribed during bone mineralization, ossification, bone metabolism, cell growth and differentiation, as well as gene products representing extracellular matrix molecules, transcription factors, and cell adhesion molecules. RESULTS EMD promoted gene expression of various osteoblast differentiation markers including a number of collagen types and isoforms, SMAD intracellular proteins, osteopontin, cadherin, alkaline phosphatase, and bone sialoprotein. EMD also upregulated a variety of growth factors including bone morphogenetic proteins, vascular endothelial growth factors, insulin-like growth factor, transforming growth factor, and their associated receptor proteins. CONCLUSION The results from the present study demonstrate that EMD is capable of activating a wide variety of genes, growth factors, and cytokines when pre-coated onto NBM particles. CLINICAL RELEVANCE The described in vitro effects of EMD on human primary osteoblasts provide further biologic support for the clinical application of a combination of EMD with NBM particles in periodontal and oral regenerative surgery.

Influence of Particle Size of Deproteinized Bovine Bone Mineral on New Bone Formation and Implant Stability after Simultaneous Sinus Floor Elevation: A Histomorphometric Study in Minipigs

BACKGROUND Deproteinized bovine bone mineral (DBBM) is one of the best-documented bone substitute materials for sinus floor elevation (SFE). PURPOSE DBBM is available in two particle sizes. Large particles are believed to facilitate improved neoangiogenesis compared with small ones. However, their impact on the rate of new bone formation, osteoconduction, and DBBM degradation has never been reported. In addition, the implant stability quotient (ISQ) has never been correlated to bone-to-implant contact (BIC) after SFE with simultaneous implant placement. MATERIALS AND METHODS Bilateral SFE with simultaneous implant placement was performed in 10 Göttingen minipigs. The two sides were randomized to receive large or small particle size DBBM. Two groups of 5 minipigs healed for 6 and 12 weeks, respectively. ISQ was recorded immediately after implant placement and at sacrifice. Qualitative histological differences were described and bone formation, DBBM degradation, BIC and bone-to-DBBM contact (osteoconduction) were quantified histomorphometrically. RESULTS DBBM particle size had no qualitative or quantitative impact on the amount of newly formed bone, DBBM degradation, or BIC for either of the healing periods (p > 0.05). Small-size DBBM showed higher osteoconduction after 6 weeks than large-size DBBM (p < 0.001). After 12 weeks this difference was compensated. There was no significant correlation between BIC and ISQ. CONCLUSION Small and large particle sizes were equally predictable when DBBM was used for SFE with simultaneous implant placement.

Five-year results evaluating the effects of platelet-rich plasma on the healing of intrabony defects treated with enamel matrix derivative and natural bone mineral

BACKGROUND Regenerative periodontal surgery using the combination of enamel matrix derivative (EMD) and natural bone mineral (NBM) with and without addition of platelet-rich plasma (PRP) has been shown to result in substantial clinical improvements, but the long-term effects of this combination are unknown. METHODS The goal of this study was to evaluate the long-term (5-year) outcomes after regenerative surgery of deep intrabony defects with either EMD + NBM + PRP or EMD + NBM. Twenty-four patients were included. In each patient, one intrabony defect was randomly treated with either EMD + NBM + PRP or EMD + NBM. Clinical parameters were evaluated at baseline and 1 and 5 years after treatment. The primary outcome variable was clinical attachment level (CAL). RESULTS The sites treated with EMD + NBM + PRP demonstrated a mean CAL change from 10.5 ± 1.6 to 6.0 ± 1.7 mm (P <0.001) at 1 year and 6.2 ± 1.5 mm (P <0.001) at 5 years. EMD + NBM-treated defects showed a mean CAL change from 10.6 ± 1.7 to 6.1 ± 1.5 mm (P <0.001) at 1 year and 6.3 ± 1.4 mm (P <0.001) at 5 years. At 1 year, a CAL gain of ≥4 mm was measured in 83% (10 of 12) of the defects treated with EMD + NBM + PRP and in 100% (all 12) of the defects treated with EMD + NBM. Compared to baseline, in both groups at 5 years, a CAL gain of ≥4 mm was measured in 75% (nine of 12 in each group) of the defects. Four sites in the EMD + PRP + NBM group lost 1 mm of the CAL gained at 1 year. In the EMD + NBM group, one defect lost 2 mm and four other defects lost 1 mm of the CAL gained at 1 year. No statistically significant differences in any of the investigated parameters were observed between the two groups. CONCLUSIONS Within their limits, the present results indicate that: 1) the clinical outcomes obtained with both treatments can be maintained up to a period of 5 years; and 2) the use of PRP does not appear to improve the results obtained with EMD + NBM.

Ten-year results following treatment of intrabony defects with an enamel matrix protein derivative combined with either a natural bone mineral or a β-tricalcium phosphate

BACKGROUND The purpose of the present study is to evaluate the 10-year results following treatment of intrabony defects treated with an enamel matrix protein derivative (EMD) combined with either a natural bone mineral (NBM) or β-tricalcium phosphate (β-TCP). METHODS Twenty-two patients with advanced chronic periodontitis and displaying one deep intrabony defect were randomly treated with a combination of either EMD + NBM or EMD + β-TCP. Clinical evaluations were performed at baseline and at 1 and 10 years. The following parameters were evaluated: plaque index, bleeding on probing, probing depth, gingival recession, and clinical attachment level (CAL). The primary outcome variable was CAL. RESULTS The defects treated with EMD + NBM demonstrated a mean CAL change from 8.9 ± 1.5 mm to 5.3 ± 0.9 mm (P <0.001) and to 5.8 ± 1.1 mm (P <0.001) at 1 and 10 years, respectively. The sites treated with EMD + β-TCP showed a mean CAL change from 9.1 ± 1.6 mm to 5.4 ± 1.1 mm (P <0.001) at 1 year and 6.1 ± 1.4 mm (P <0.001) at 10 years. At 10 years two defects in the EMD + NBM group had lost 2 mm, whereas two other defects had lost 1 mm of the CAL gained at 1 year. In the EMD + β-TCP group three defects had lost 2 mm, whereas two other defects had lost 1 mm of the CAL gained at 1 year. Compared with baseline, at 10 years, a CAL gain of ≥3 mm was measured in 64% (i.e., seven of 11) of the defects in the EMD + NBM group and in 82% (i.e., nine of 11) of the defects in the EMD + β-TCP group. No statistically significant differences were found between the 1- and 10-year values in either of the two groups. Between the treatment groups, no statistically significant differences in any of the investigated parameters were observed at 1 and 10 years. CONCLUSION Within their limitations, the present findings indicate that the clinical improvements obtained with regenerative surgery using EMD + NBM or EMD + β-TCP can be maintained over a period of 10 years.

Bone mineral density and circulating biomarkers in the BIG 1-98 trial comparing adjuvant letrozole, tamoxifen and their sequences.

The purpose of the study is to determine the effects of the BIG 1-98 treatments on bone mineral density. BIG 1-98 compared 5-year adjuvant hormone therapy in postmenopausal women allocated to four groups: tamoxifen (T); letrozole (L); 2-years T, 3-years L (TL); and 2-years L, 3-years T (LT). Bone mineral density T-score was measured prospectively annually by dual energy X-ray absorption in 424 patients enrolled in a sub-study after 3 (n = 150), 4 (n = 200), and 5 years (n = 74) from randomization, and 1 year after treatment cessation. Prevalence of osteoporosis and the association of C-telopeptide, osteocalcin, and bone alkaline phosphatase with T-scores were assessed. At 3 years, T had the highest and TL the lowest T-score. All arms except for LT showed a decline up to 5 years, with TL exhibiting the greatest. At 5 years, there were significant differences on lumbar T-score only between T and TL, whereas for femur T-score, differences were significant for T versus L or TL, and L versus LT. The 5-year prevalence of spine and femur osteoporosis was the highest on TL (14.5 %, 7.1 %) then L (4.3 %, 5.1 %), LT (4.2 %, 1.4 %) and T (4 %, 0). C-telopeptide and osteocalcin were significantly associated with T-scores. While adjuvant L increases bone mineral density loss compared with T, the sequence LT has an acceptable bone safety profile. C-telopeptide and osteocalcin are useful markers of bone density that may be used to monitor bone health during treatment. The sequence LT may be a valid treatment option in patients with low and intermediate risk of recurrence.

Impact of Switching From Zidovudine to Tenofovir Disoproxil Fumarate on Bone Mineral Density and Markers of Bone Metabolism in Virologically Suppressed HIV-1 Infected Patients; A Substudy of the PREPARE Study

Context: In virologically suppressed, antiretroviral-treated patients, the effect of switching to tenofovir (TDF) on bone biomarkers compared to patients remaining on stable antiretroviral therapy is unknown. Methods: We examined bone biomarkers (osteocalcin [OC], procollagen type 1 amino-terminal propeptide, and C-terminal cross-linking telopeptide of type 1 collagen) and bone mineral density (BMD) over 48 weeks in virologically suppressed patients (HIV RNA < 50 copies/ml) randomized to switch to TDF/emtricitabine (FTC) or remain on first-line zidovudine (AZT)/lamivudine (3TC). PTH was also measured. Between-group differences in bone biomarkers and associations between change in bone biomarkers and BMD measures were assessed by Student's t tests, Pearson correlation, and multivariable linear regression, respectively. All data are expressed as mean (SD), unless otherwise specified. Results: Of 53 subjects (aged 46.0 y; 84.9% male; 75.5% Caucasian), 29 switched to TDF/FTC. There were reductions in total hip and lumbar spine BMD in those switching to TDF/FTC (total hip, TDF/FTC, −1.73 (2.76)% vs AZT/3TC, −0.39 (2.41)%; between-group P = .07; lumbar spine, TDF/FTC, −1.50 (3.49)% vs AZT/3TC, +0.25 (2.82)%; between-group P = .06), but they did not reach statistical significance. Greater declines in lumbar spine BMD correlated with greater increases in OC (r = −0.28; P = .05). The effect of TDF/FTC on bone biomarkers remained significant when adjusted for baseline biomarker levels, gender, and ethnicity. There was no difference in change in PTH levels over 48 weeks between treatment groups (between-group P = .23). All biomarkers increased significantly from weeks 0 to 48 in the switch group, with no significant change in those remaining on AZT/3TC (between-group, all biomarkers, P < .0001). Conclusion: A switch to TDF/FTC compared to remaining on a stable regimen is associated with increases in bone turnover that correlate with reductions in BMD, suggesting that TDF exposure directly affects bone metabolism in vivo.

Bone mineral density (BMD) and computer tomographic measurements of the equine proximal phalanx in correlation with breaking strength

Despite the fact that bone mineral density (BMD) is an important fracture risk predictor in human medicine, studies in equine orthopedic research are still lacking. We hypothesized that BMD correlates with bone failure and fatigue fractures of this bone. Thus, the objectives of this study were to measure the structural and mechanical properties of the proximal phalanx with dual energy X-ray absorptiometry (DXA), to correlate the data obtained from DXA and computer tomography (CT) measurements to those obtained by loading pressure examination and to establish representative region of interest (ROI) for in vitro BMD measurements of the equine proximal phalanx for predicting bone failure force. DXA was used to measure the whole bone BMD and additional three ROI sites in 14 equine proximal phalanges. Following evaluation of the bone density, whole bone, cortical width and area in the mid-diaphyseal plane were measured on CT images. Bones were broken using a manually controlled universal bone crusher to measure bone failure force and reevaluated for the site of fractures on follow-up CT images. Compressive load was applied at a constant displacement rate of 2 mm/min until failure, defined as the first clear drop in the load measurement. The lowest BMD was measured at the trabecular region (mean +/- SD: 1.52 +/- 0.12 g/cm2; median: 1.48 g/cm2; range: 1.38-1.83 g/cm2). There was a significant positive linear correlation between trabelcular BMD and the breaking strength (P = 0.023, r = 0.62). The trabecular region of the proximal phalanx appears to be the only significant indicator of failure of strength in vitro. This finding should be reassessed to further reveal the prognostic value of trabecular BMD in an in vivo fracture risk model.

Effects of zoledronate versus placebo on spine bone mineral density and microarchitecture assessed by the trabecular bone score in postmenopausal women with osteoporosis: a three-year study

The trabecular bone score (TBS) is an index of bone microarchitectural texture calculated from anteroposterior dual-energy X-ray absorptiometry (DXA) scans of the lumbar spine (LS) that predicts fracture risk, independent of bone mineral density (BMD). The aim of this study was to compare the effects of yearly intravenous zoledronate (ZOL) versus placebo (PLB) on LS BMD and TBS in postmenopausal women with osteoporosis. Changes in TBS were assessed in the subset of 107 patients recruited at the Department of Osteoporosis of the University Hospital of Berne, Switzerland, who were included in the HORIZON trial. All subjects received adequate calcium and vitamin D3. In these patients randomly assigned to either ZOL (n = 54) or PLB (n = 53) for 3 years, BMD was measured by DXA and TBS assessed by TBS iNsight (v1.9) at baseline and 6, 12, 24, and 36 months after treatment initiation. Baseline characteristics (mean ± SD) were similar between groups in terms of age, 76.8 ± 5.0 years; body mass index (BMI), 24.5 ± 3.6 kg/m(2) ; TBS, 1.178 ± 0.1 but for LS T-score (ZOL-2.9 ± 1.5 versus PLB-2.1 ± 1.5). Changes in LS BMD were significantly greater with ZOL than with PLB at all time points (p < 0.0001 for all), reaching +9.58% versus +1.38% at month 36. Change in TBS was significantly greater with ZOL than with PLB as of month 24, reaching +1.41 versus-0.49% at month 36; p = 0.031, respectively. LS BMD and TBS were weakly correlated (r = 0.20) and there were no correlations between changes in BMD and TBS from baseline at any visit. In postmenopausal women with osteoporosis, once-yearly intravenous ZOL therapy significantly increased LS BMD relative to PLB over 3 years and TBS as of 2 years.