Nonosteoporotic Postmenopausal Women Research Articles

17ß-Oestradiol and 1a, 25-dihydroxy;-cholecalciferol modulate constitutive and bone matrix-induced interleukin-1ß (IL-1ß) production by peripheral blood mononuclear cells isolated from postmenopausal women

Local production and release of interleukin-1 (IL-1) may be of importance for bone remodeling, since this cytokine is known to stimulate bone resorption. We have studied the effect of bone matrix constituents on IL-1 beta production by peripheral blood mononuclear cells (PBMCs) isolated from 20 postmenopausal non-osteoporotic women. Hydroxyapatite (0.5 mg/ml) and heat-denaturated collagen (25 micrograms/ml) stimulated IL-1 beta production 5-fold and 520-fold, respectively, compared to control (p < 0.01). In contrast, transforming growth factor-beta (TGF-beta, 10 ng/ml), a cytokine which is abundant in bone matrix, suppressed median IL-1 beta release to 13% of control value (p < 0.01). The bone matrix-induced changes in IL-1 beta production were modulated by 10 nmol/1 17 beta-oestradiol and 10 nmol/1 1 alpha,25-dihydroxy-cholecalciferol (1,25(OH)2D3). Specifically, 17 beta oestradiol stimulated constitutive IL-1 beta release with 89% (p < 0.01) and nullified the suppressive effect of TGF-beta. Moreover, 1,25(OH)2D3 had a synergistically stimulatory effect with both hydroxyapatite and collagen, although there was no effect of this hormone when added alone. The adherent cells were slightly more elongated after treatment with 1,25(OH)2D3 and collagen, while TGF-beta and 17 beta-oestradiol had no effect on cellular morphology. Addition of hydroxyapatite resulted in long and spindle-shaped cells, and phagocytosis of the particles occurred. The modulatory effects of oestrogen and vitamin D on constitutive and bone-matrix induced IL-1 beta production by PBMCs may be of importance for bone remodelling during postmenopausal bone loss and at a site of fracture.

Vitamin D and HRT: No benefit additional to that of HRT alone in prevention of bone loss in early postmenopausal women. A 2.5-year randomized placebo-controlled study

The study was designed to examine the effect of hormone replacement therapy (HRT) and low-dose vitamin D (Vit D) supplementation on the prevention of bone loss in non-osteoporotic early postmenopausal women and to determine whether Vit D supplementation can give additional benefit to an already optimized estrogen regimen. The effects of HRT and Vit D on bone mineral density (BMD) were studied in postmenopausal women in a 2.5-year randomized placebo-controlled study. The study population was a subgroup of the Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE) (n=13100). A total of 464 early postmenopausal women were randomized to four groups: (1) HRT (a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate (E2Val/CPA); (2) vitamin D3 (cholecalciferol, 300 IU/day); (3) HRT+Vit D; and (4) placebo (calcium lactate; 93 mg Ca2+/day). Lumbar (L1–4) and femoral neck BMD were determined by dual-energy X-ray absorptiometry before and after 2.5 years of treatment. After 2.5 years, lumbar BMD had increased by 1.8% in the HRT group (p<0.001) and by 1.4% in the HRT+Vit D group (p=0.002), whereas lumbar BMD had decreased by 3.5% (p<0.001) in the Vit D group and by 3.7% (p<0.001) in the placebo group. The loss of femoral neck BMD was lower in the HRT (−0.3%) and the HRT+Vit D (−0.9%) groups compared with the Vit D (−2.4%) and the placebo groups (−3.7%). This study confirms the beneficial effect of HRT on BMD. It also shows that low-dose vitamin D supplementation has only a minor effect in the prevention of osteoporosis in non-osteoporotic early postmenopausal women and does not give any benefit additional to that of HRT alone.

Bone resorption at the femoral neck is dependent on local factors in nonosteoporotic late postmenopausal women: An in vitro-in vivo study

Local mediators of bone resorption may be involved in bone loss in recently postmenopausal women and in osteoporosis. In the present study, we investigated the production of cytokines and the formation of osteoclast-like cells in marrow cultures from 16 late postmenopausal nonosteoporotic women (mean age: 66 +/- 8 years; time after menopause: 15 +/- 8 years) undergoing hip replacement for arthrosis. Marrow adherent mononuclear cells (MMNC) isolated from femoral diaphysis marrow were cultured for 10 days in the absence or in the presence of 1,25(OH)2D3. In vivo bone resorption was concomitantly assessed by histomorphometry on femoral neck bone sections. The number of TRAP+ multinucleated cells obtained after 10 days in MMNC cultured in the presence of 1,25(OH)2D3 correlated with the number of osteoclasts measured on the bone femoral neck biopsies (r = 0.65, p < 0.01), suggesting that the formation of multinucleated cells in vitro could reflect the osteoclast differentiation in vivo. Furthermore, the number of osteoclasts was related to the eroded volume and the trabecular separation of the femoral neck bone biopsies. Finally, the release of interleukin-1 (IL-1), IL-6, and TNF-alpha by cultures of peripheral blood mononuclear cells (PBMC) and MMNC was measured by radioimmunoassay. The cytokine levels of basal and 1,25(OH)2D3-treated MMNC decreased from days 2 to 5 and then reached a plateau to day 10. The number of TRAP+ multinucleated cells obtained after 10 days in MMNC cultures correlated with the basal IL-6 release in the same cultures determined at day 2 (r = 0.55, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Skeletal muscle mechanics in osteoporotic and nonosteoporotic postmenopausal women.

The purpose of this study was to evaluate single-joint, dynamic muscle function of osteoporotic (OST) and nonosteoporotic (N-OST) women. Knee flexor and extensor function in postmenopausal women (6th decade OST, n = 15; 7th decade OST, n = 10; 6th decade N-OST, n = 6; 7th decade N-OST, n = 5) were evaluated at five angular velocities from 60 degrees.s-1 to 300 degrees.s-1. All subject groups had similar anthropometric measurements, but the 6th decade N-OST group were more physically active than the age-matched OST group. The OST and N-OST women produced peak torque at similar knee angles. The 6th decade N-OST women produced significantly greater knee extensor mean peak torque and angle specific torque, and mean work than any of the other three groups (P < 0.05). However, knee flexor function was equivalent throughout the groups for most comparisons, except those between the 6th decade N-OST and 7th decade OST. While previous research has shown an early loss of flexor muscle function in aging women, our data indicated that women with osteoporosis also experience a deterioration in quadriceps muscle function not encountered within the N-OST subjects. It is possible that such a change is precipitated by reduced physical activity, and may mirror deterioration in bone mineral content.

Cytokine production and surface antigen expression by peripheral blood mononuclear cells in postmenopausal osteoporosis

It was reported earlier that IL-1 production by cultured monocytes and the ratio of helper (CD4) to suppressor (CD8) lymphocytes in peripheral blood are different in osteoporotic compared to nonosteoporotic subjects. We examined these and several other parameters related to the biosynthetic activity and differentiation status of peripheral blood mononuclear cells (PBMC) in untreated osteoporotic postmenopausal women (age 65 +/- 7, n = 46), nonosteoporotic postmenopausal women (age 55 +/- 3, n = 20), and nonosteoporotic premenopausal women (age 37 +/- 7, n = 8), as defined by spine density. We found that unstimulated monocytes from osteoporotics did not produce detectable IL-1 beta as determined by ELISA. In addition, there were no significant differences between osteoporotics and nonosteoporotics in IL-1 beta or IFN-gamma production by PBMC stimulated with OKT3, a monoclonal antibody to the T cell-receptor complex. The proliferative response of lymphocytes to OKT3 was significantly less (p < 0.02) in osteoporotics compared to nonosteoporotic post- and premenopausal women; multiple-regression analysis, however, indicated that this difference was not due to bone density but to age. Flow cytometric analysis of PBMC revealed no difference between osteoporotics and nonosteoporotics in the distribution of 18 phenotypic subsets determined, including CD4- or CD8-positive lymphocytes or the ratio of CD4 to CD8 cells. Further, there was no correlation of the surface markers with bone density, the exceptions being the subsets expressing the CD3/CD56 and CD8/CD56 markers, which were inversely related to spine density in the osteoporotic women.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum concentrations of estrogen, testosterone, and gonadotropins in osteoporotic and nonosteoporotic postmenopausal women.

In a group of women with vertebral compression fractures due to postmenopausal osteoporosis, values for plasma testosterone, serum estrogen, and serum gonadotropins were not significantly different from those in an agematched control group. The results do not support the suggestion that women in whom clinically apparent osteoporosis develops postmenopausally have a greater postmenopausal decline in sex hormone production. We conclude that some factor (or factors) in addition to the menopause is present in osteoporotic patients that accelerates bone loss.

Treatment of postmenopausal osteoporosis with oestrogens and androgens.

ABSTRACT Fifteen patients with postmenopausal osteoporosis and 51 postmenopausal women without osteoporosis were subjected to intermittent treatment with oestrogens and androgens during 2 to 8 years. In the patients with osteoporosis there was prior to treatment a considerable loss of height which ceased more or less during therapy. In the nonosteoporotic postmenopausal women there was a negligible reduction in height during treatment in comparison to control cases of the same age group.