A randomized study on the effects of estrogen/gestagen or high dose oral calcium on trabecular bone remodeling in postmenopausal osteoporosis

Steiniche, Torben; Hasling, C; Charles, Peder; Eriksen, Erik Fink; Mosekilde, Leif; Melsen, F.

doi:10.1016/8756-3282(89)90126-9

Cited by 189 publications

(69 citation statements)

References 35 publications

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“…Studies that have been performed have, most frequently, been substudies of larger clinical trials and have used paired iliac crest bone biopsies with 2D histomorphometric analysis of the biopsy specimens, with only recently the application of the CT technique for a more specific 3D assessment of iliac crest trabecular microarchitecture. In response to estradiol (22) or estradiol/norethisterone (23) therapy, no significant change in BV/TV, and either no significant change (23) or a decrease (22) in wall thickness, was noted after paired iliac crest bone biopsy histomorphometric analysis in 22-28 postmenopausal osteopenic or osteoporotic women studied for 1-2 years. In response to bisphosphonate treatment, preservation of trabecular microarchitecture (BV/TV, trabecular number and spacing, trabecular thickness, and connectivity density), similar to that seen at the radius and hip in this study, was noted in 14 postmenopausal osteopenic women in response to 1 year of risedronate treatment as determined by CT analysis of paired iliac crest bone biopsy specimens (24) ; in 12 placebo control subjects significant deterioration of these microarchitecture parameters was noted.…”

Section: Discussionmentioning

confidence: 91%

Effects of Salmon Calcitonin on Trabecular Microarchitecture as Determined by Magnetic Resonance Imaging: Results From the QUEST Study

Chesnut

Majumdar²,

Newitt³

et al. 2005

Journal of Bone and Mineral Research

160

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The unique noninvasive MRI technique was used to assess trabecular microarchitecture at multiple skeletal sites in 91 postmenopausal osteoporotic women receiving nasal spray salmon calcitonin (CT-NS) or placebo over 2 years. In the distal radius and lower trochanter of the hip, individuals treated with CT-NS exhibited significant preservation of trabecular bone microarchitecture compared with placebo, where significant deterioration was shown. MRI analyses of os calcis or µCT/histomorphometric analyses of bone biopsies did not reveal consistent differences in architecture between CT-NS and placebo.Introduction: It is postulated that the reduction in osteoporotic fracture risk in response to certain antiresorptive osteoporosis therapies is caused less by effects on bone quantity than on bone quality (specifically trabecular microarchitecture). To test this hypothesis, the QUEST study was conducted to assess the effects of nasal spray salmon calcitonin (CT-NS) or placebo on parameters of trabecular microarchitecture at multiple skeletal sites using noninvasive MRI technology and iliac crest bone biopsies by CT/histomorphometry. Materials and Methods: Ninety-one postmenopausal osteoporotic women were followed for 2 years (n ‫ס‬ 46 for CT-NS, n ‫ס‬ 45 for placebo); all women received 500 mg calcium daily. MRI measurements at distal radius, hip (T2 relaxation time [T2*]), and os calcis (obtained yearly), iliac crest bone biopsies with 2D histomorphometry and 3D CT (obtained at study onset and conclusion), DXA-BMD at spine/hip/wrist/os calcis (obtained yearly), and markers of bone turnover (obtained at 2-week to 12-month intervals) were analyzed, with an analysis of covariance model used to assess treatment effect for parameters of interest. Results and Conclusions: MRI assessment of trabecular microarchitecture at individual regions of the distal radius revealed significant improvement, or preservation (no significant loss), in the CT-NS-treated group compared with significant deterioration in the placebo control group, as reflected in apparent BV/TV (p < 0.03), apparent trabecular number (p < 0.01), and apparent trabecular spacing (p < 0.01). Also, at the hip, the CT-NS group exhibited preservation of trabecular microarchitecture at the lower trochanter (p < 0.05) as determined by T2* MRI technology. Significant deterioration of trabecular bone architecture was noted in the placebo group at the femoral neck, Ward's triangle, and lower trochanteric sites. Apart from a significant increase in apparent trabecular number in the CT-NS group, significant changes within or between groups were not noted at the os calcis. Combined CT/histomorphometric analysis of iliac crest bone biopsies did not reveal significant differences between treated and placebo groups. In the CT-NS group, regardless of the change in BMD (gain or loss) at the spine, hip, or distal radius, preservation of parameters of trabecular microarchitecture was noted, whereas in the placebo group, regardless of the change in BMD (gain or loss) at the...

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Section: Discussionmentioning

confidence: 91%

Effects of Salmon Calcitonin on Trabecular Microarchitecture as Determined by Magnetic Resonance Imaging: Results From the QUEST Study

Chesnut

Majumdar²,

Newitt³

et al. 2005

Journal of Bone and Mineral Research

160

View full text Add to dashboard Cite

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“…Both bone resorption and bone forma- tion rates are elevated, and the resulting bone loss indicates that resorption exceeds formation (48,49). Estrogen replacement therapy decreases bone resorption and prevents bone loss (50, 5 1 ), primarily by suppressing the rate ofremodeling activation (52). In view of these findings, pharmacological agents that reduce bone resorption and thus bone turnover should have similar effects on the bone loss caused by estrogen deficiency (53)(54)(55)(56).…”

Section: Discussionmentioning

confidence: 99%

The effects of 2-year treatment with the aminobisphosphonate alendronate on bone metabolism, bone histomorphometry, and bone strength in ovariectomized nonhuman primates.

Balena¹,

Toolan²,

Shea³

et al. 1993

J. Clin. Invest.

370

170

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This study examined the effect of 2 yr of treatment with the aminobisphosphonate alendronate (ALN) (0.05 or 0.25 mg/ kg i.v. ALN every 2 wk) on estrogen deficiency bone loss and bone strength changes in ovariectomized (OVX) baboons (n = 7 per group) and the ALN mode of action at the tissue level. Biochemical markers of bone turnover increased in OVX animals and were maintained by ALN treatment at non-OVX levels (low dose) or below (high dose). 2 yr of treatment produced no cumulative effects on bone turnover markers. Histomorphometry showed a marked increase in cancellous bone remodeling in OVX animals. Activation frequency increased from 0.48 to 0.86 per yr (L5 vertebra), and the osteoid surfaces from 9 to 13.5% (P < 0.05). No changes were observed in eroded and osteoclast surfaces. ALN treatment decreased activation frequency and indices of bone formation to control levels (low dose) or below (high dose), did not change indices of mineralization, and increased bone mineral density (BMD) in the lumbar vertebrae (L2-L4) by 15% at 0.25 mg/kg (P < 0.05), relative to vehicle-treated animals. The mean strength of cancellous bone (LA) increased by 44% (low ALN dose) and 100% (high dose), compared with vehicle. The strength of individual bones correlated with the square of the L2-L4 BMD (r = 0.91, P < 0.0034). In conclusion, ALN treatment reversed the effects of ovariectomy on cancellous bone turnover and increased bone mass and bone strength in baboons. (J. Clin. Invest. 1993. 92:2577-2586 Key words: osteoporosis * alendronate * histomorphometry-bone strength * bone mineral density

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“…Wall thickness is a measure of the amount of bone formed in a remodeling packet of cells and is determined by the number and activity of osteoblasts at the remodeling site. Considerable evidence suggests that the decline in wall thickness is due to the aging process itself, as opposed to hormone changes that occur with advancing age, such as alterations in the level of sex steroids or parathyroid hormone (18,19). Hence, the osteopenia due to aging may be due to a deficit in the number of osteoblasts recruited to the remodeling site relative to the demand for them (17).…”

Section: Introductionmentioning

confidence: 99%

Linkage of decreased bone mass with impaired osteoblastogenesis in a murine model of accelerated senescence.

Jilka¹,

Weinstein²,

Takahashi³

et al. 1996

J. Clin. Invest.

315

263

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Bone marrow is the principal site for osteoclastogenesis and osteoblastogenesis; and an increase in the former has been linked with bone loss caused by acute loss of gonadal steroids. We have now used an established murine model of accelerated senescence and osteopenia (SAMP6) to test the hypothesis that reduced osteoblastogenesis is linked with decreased bone mass. At 1 mo of age, the number of osteoblast progenitors in SAMP6 marrow was indistinguishable from controls; however a threefold decrease was found at 3-4 mo of age. Impaired osteoblast formation was temporally associated with decreased bone formation and decreased bone mineral density, as determined by histomorphometric analysis of tetracycline-labeled cancellous bone and dualenergy x-ray absorptiometry, respectively. Osteoclastogenesis determined in ex vivo bone marrow cultures was also decreased in these mice, as was the number of osteoclasts in histologic sections. Moreover, unlike controls, senescenceaccelerated mice failed to increase osteoclast development after gonadectomy. The osteoclastogenesis defect was secondary to impaired osteoblast formation as evidenced by the fact that osteoclastogenesis could be restored by addition of osteoblastic cells from normal mice. These findings provide the first demonstration of a link between low bone mineral density and decreased osteoblastogenesis in the bone marrow and validate the senescence-accelerated mouse as a model of involutional osteopenia. ( J. Clin. Invest. 1996.

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A randomized study on the effects of estrogen/gestagen or high dose oral calcium on trabecular bone remodeling in postmenopausal osteoporosis

Cited by 189 publications

References 35 publications

Effects of Salmon Calcitonin on Trabecular Microarchitecture as Determined by Magnetic Resonance Imaging: Results From the QUEST Study

Effects of Salmon Calcitonin on Trabecular Microarchitecture as Determined by Magnetic Resonance Imaging: Results From the QUEST Study

The effects of 2-year treatment with the aminobisphosphonate alendronate on bone metabolism, bone histomorphometry, and bone strength in ovariectomized nonhuman primates.

Linkage of decreased bone mass with impaired osteoblastogenesis in a murine model of accelerated senescence.

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