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R Civitelli

Publications and source records attributed to R Civitelli.

At least 55 records · Page 3Linked to original sources
PubMed1994

Interleukin-4 inhibits bone resorption and acutely increases cytosolic Ca2+ in murine osteoclasts.

Interleukin-4 (IL-4) is an immune cytokine recently shown to inhibit bone resorption. To determine whether IL-4 directly acts on osteoclasts, we have analyzed its effect on cytosolic calcium concentration [Ca2+]i and bone resorptive function of murine osteoclastic cells generated from bone marrow/stromal cell co-cultures. IL-4 exposure induced an immediate and sustained increase in [Ca2+]i that remained elevated for at least 10 min. This IL-4 effect was dose-dependent, with the maximal effect (209 +/- 15% of baseline, n = 16) at 200 units/ml and an apparent ED0.5 of 60 units/ml. The IL-4-induced [Ca2+]i rise required extracellular Ca2+ influx, since the response was prevented by LaCl3, and voltage-gated Ca2+ channel blockers, although the IL-4 effect was more sensitive to nicardipine and nifedipine than to diltiazem. Depolarization by high extracellular K+ concentration also raised [Ca2+]i, and, under these conditions, osteoclasts failed to respond to IL-4. On the other hand, when intracellular Ca2+ stores were depleted by thapsigargin, IL-4 still induced an increase in [Ca2+]i, although smaller in amplitude and transient. Calcitonin also produced [Ca2+]i increases in osteoclasts, yet it only slightly desensitized these cells to IL-4. Furthermore, IL-4 was much less effective on osteoclasts pretreated (5-10 min) with either forskolin or 8-bromo-cAMP. Both IL-4 and calcitonin were effective even when [Ca2+]i had been increased by exposure to high extracellular Ca2+. Finally, IL-4 dose dependently inhibited the bone-resorptive activity of mature osteoclasts. Therefore, IL-4 signal transduction in osteoclasts involves a rapid and sustained elevation of [Ca2+]i mediated by a voltage-dependent Ca2+ influx, in combination with Ca2+ release from intracellular stores. Modulation of osteoclast [Ca2+]i represents a potential mechanism by which IL-4 inhibits bone resorption.

Animals↗
PubMed1994

Connexin43 and connexin45 form gap junctions with different molecular permeabilities in osteoblastic cells.

We examined the expression and function of gap junctions in two rat osteoblastic cell lines, ROS 17/2.8 and UMR 106-01. The pattern of expression of gap junction proteins in these two cell lines was distinct: ROS cells expressed only connexin43 on their cell surface, while UMR expressed predominantly connexin45. Immunoprecipitation and RNA blot analysis confirmed the relative quantitation of these connexins. Microinjected ROS cells passed Lucifer yellow to many neighboring cells, but UMR cells were poorly coupled by this criterion. Nevertheless, both UMR and ROS cells were electrically coupled, as characterized by the double whole cell patch-clamp technique. These studies suggested that Cx43 in ROS cells mediated cell-cell coupling for both small ions and larger molecules, but Cx45 in UMR cells allowed passage only of small ions. To demonstrate that the expression of different connexins alone accounted for the lack of dye coupling in UMR cells, we assessed dye coupling in UMR cells transfected with either Cx43 or Cx45. The UMR/Cx43 transfectants were highly dye coupled compared with the untransfected UMR cells, but the UMR/Cx45 transfectants demonstrated no increase in dye transfer. These data demonstrate that different gap junction proteins create channels with different molecular permeabilities; they suggest that different connexins permit different types of signalling between cells.

Animals↗
PubMed1994

Single-cell analysis of cyclic AMP response to parathyroid hormone in osteoblastic cells.

We previously demonstrated that the [Ca2+]i response to PTH is heterogeneous in single UMR-106-01 osteogenic sarcoma cells. To verify whether response heterogeneity is a universal feature of PTH signal transduction, cAMP production was monitored in monolayer cultures of UMR-106-01 cells and human trabecular bone osteoblasts (HOB) using the cAMP-sensitive fluorescent indicator FlCRhR. FlCRhR was microinjected into single cells, and the 500-530/> 560 nm fluorescence ratio was monitored by confocal laserscanning video imaging as a measure of cAMP concentration ([cAMP]). Virtually all UMR-106-01 cells exposed to bovine PTH(1-34) (10(-7) M) exhibited an increase in intracellular [cAMP], with an average fluorescence ratio change of 145 +/- 17% of baseline (n = 15), corresponding to nearly maximal dissociation of protein kinase A. In the continued presence of the hormone (10(-7) M), [cAMP] remained elevated for at least 30 minutes. This effect was accompanied by a slow translocation of the fluorescein-labeled catalytic subunit of protein kinase A from the cytoplasm to the nucleus. In contrast, PTH(1-34) caused no detectable increase in [cAMP] in HOB cells, although PGE2 (3 x 10(-6) M) stimulation was able to increase the FlCRhR ratio (154 +/- 27%, n = 10). The truncated fragment PTH(2-34) was only 67% as potent at PTH(1-34), but deletion of the first two amino acids at the N terminus abolished the hormone's ability to stimulate cAMP production in UMR-106-01 cells. Brief exposure to 10(-7) M of either PTH(3-34) or PTH(7-34) did not affect the amplitude of the fluorescence ratio change induced by equimolar doses of PTH(1-34). Thus, in osteoblast-like cells stimulated with PTH, the [cAMP] response is much more homogeneous from cell to cell than the [Ca2+]i response.

Animals↗
PubMed1994

Stimulation of human osteoblast differentiation and function by ipriflavone and its metabolites.

Ipriflavone (IP), an isoflavone derivative, has been shown to interfere with bone remodeling by inhibiting bone resorption and perhaps stimulating bone formation. In this study, we have analyzed the effect of IP and its metabolites on the differentiation and function of human osteoblastic cells. Bone marrow stromal osteoprogenitor cells (BMC) and trabecular bone osteoblasts (HOB) were isolated from human donors. The former can be induced to differentiate by treatment with dexamethasone, whereas the latter represent a more differentiated osteoblast. Incubation of BMC with metabolite III (10(-5) M) for 1 week induced modest but significant changes of alkaline phosphatase activity. Though both IP and metabolite III stimulated the expression of bone sialoprotein mRNA, a protein involved in cell attachment to the matrix, only metabolite III increased the steady-state level of decorin mRNA, a collagen fibrillogenesis-regulating proteoglycan. Metabolites III and V, but not the other isoflavones, increased the expression of type I collagen mRNA in HOB, whereas no detectable changes were observed in BMC cells with any of the experimental compounds. In HOB, an increased abundance of osteopontin and bone sialoprotein mRNA were also obtained after 1-week treatment with IP or metabolite V. No appreciable effects of IP or its metabolites were seen on osteocalcin expression and synthesis by either cell type. Finally, IP consistently increased the amount of 45Ca incorporated into the cell layer by BMC, and stimulated mineralization of both BMC and HOB, assessed by von Kossa staining. Thus, IP and its metabolites regulate the differentiation and biosynthetic properties of human bone-forming cells by enhancing the expression of some important matrix proteins and facilitating the mineralization process.

Alkaline Phosphatase↗
PubMed1994

Activation of the Ca2+ message system by parathyroid hormone is dependent on the cell cycle.

To verify whether the heterogeneous intracellular calcium ([Ca2+]i) responses to PTH observed in the UMR 106-01 osteogenic sarcoma cells are secondary to cell cycle asynchrony or to genotypic differences within the population, we synchronized cell monolayers at the G1/S boundary using a sequential thymidine-aphidicolin block. Video image analysis of fura-2-loaded cells revealed that PTH (10(-7) M) induced transient increases of [Ca2+]i preferentially in cells in S phase (82% response frequency, n = 63; 286 +/- 33% of baseline, n = 29), whereas cells in G1 phase responded poorly to PTH (10% response frequency, n = 51; 140 +/- 8% of baseline, n = 5). In contrast, cell exposure to 2% fetal calf serum was followed by [Ca2+]i transients in 83% (n = 42) of cells in G1 phase, but in only 25% (n = 63) of cells in S phase, with similar response amplitude. Hormonal responsiveness was heterogeneous in small clones obtained from single UMR 106-01 cells, with response frequency similar to that observed in nonsynchronized cultures. Pretreatment with either La3+, nifedipine, or pertussis toxin reduced both frequency and amplitude of PTH response in S phase to levels close to G1 phase, whereas there was no significant difference in inositol trisphosphate generated by PTH stimulation in either phase. Therefore, the heterogeneous [Ca2+]i responses of UMR 106-01 cells to hormonal stimulation is dependent on the phase of the cell cycle, rather than on genotypic heterogeneity. The switch from the G1 to the S phase mode of response is driven by active coupling between the PTH receptor and a Ca2+ channel through a pertussis toxin-sensitive G protein.

Animals↗
PubMed1993

Desensitization of calcium messenger system in parathyroid hormone-stimulated opossum kidney cells.

We have studied the desensitization of the calcium message system to parathyroid hormone (PTH) by monitoring intracellular calcium concentration ([Ca2+]i) in an opossum kidney cell line (OKP). PTH (10(-7) M) caused a transient increase in [Ca2+]i, with an average peak height of 48.7 +/- 4.7% above baseline (n = 32). Cells stimulated with either 10(-7) or 10(-8) M PTH did not respond to a second challenge with a maximal dose (10(-7) M) of the hormone, whereas lower concentrations of PTH (10(-9) M and 10(-10) M) only partially desensitized the cells, since a [Ca2+]i transient of smaller amplitude (12.7 +/- 2.1 and 40.6 +/- 6.2% above baseline, respectively) was observed with a second stimulation. Desensitization developed within 5 min of initial hormone exposure, when PTH receptor binding was not significantly decreased. Maximal reduction of PTH binding sites (37.0 +/- 1.4%) was achieved only after 2 h. Partial desensitization was reproduced by 10(-9) M phorbol 12-myristate 13-acetate (PMA) but not by dibutyryladenosine 3',5'-cyclic monophosphate, and it was blocked by staurosporine. However, staurosporine had no effect on the complete desensitization induced by high doses of PTH. At 10(-9) M, PTH also caused a time-dependent desensitization of the adenosine 3',5'-cyclic monophosphate (cAMP) response, with maximal inhibition achieved after 2 h. PMA also decreased the cAMP response to PTH, but its inhibitory effect was less potent than that of 10(-9) M PTH. Therefore PTH induces a dose-dependent homologous desensitization of the Ca2+ message system in OKP cells, independent of receptor occupancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗
PubMed1993

Connexin43 mediates direct intercellular communication in human osteoblastic cell networks.

We have examined cell coupling and expression of gap junction proteins in monolayer cultures of cells derived from human bone marrow stromal cells (BMC) and trabecular bone osteoblasts (HOB), and in the human osteogenic sarcoma cell line, SaOS-2. Both HOB and BMC cells were functionally coupled, since microinjection of Lucifer yellow resulted in dye transfer to neighboring cells, with averages of 3.4 +/- 2.8 (n = 131) and 8.1 +/- 9.3 (n = 51) coupled cells per injection, respectively. In contrast, little diffusion of Lucifer yellow was observed in SaOS-2 monolayers (1.4 +/- 1.8 coupled cells per injection, n = 100). Dye diffusion was inhibited by octanol (3.8 mM), an inhibitor of gap junctional communication. All of the osteoblastic cells expressed mRNA for connexin43 and connexin45, but not for connexins 26, 32, 37, 40, or 46. Whereas all of the osteoblastic cells expressed similar quantities of mRNA for connexin43, the poorly coupled SaOS-2 cells produced significantly less Cx43 protein than either HOB or BMC, as assessed by immunofluorescence and immunoprecipitation. Conversely, more Cx45 mRNA was expressed by SaOS-2 cells than by HOB or BMC. Thus, intercellular coupling in normal and transformed human osteoblastic cells correlates with the level of expression of Cx43, which appears to mediate intercellular communication in these cells. Gap junctional communication may serve as a means by which osteoblasts can work in synchrony and propagate locally generated signals throughout the skeletal tissue.

Alkaline Phosphatase↗
PubMed1992

An effective regimen of intranasal salmon calcitonin in early postmenopausal bone loss.

In order to devise a convenient and effective therapeutic regimen of intranasal salmon calcitonin (sCT) for the treatment of early postmenopausal bone loss, we studied the effects of a 1-year course of sCT nasal spray on vertebral mineral content (VMC), assessed by dual photon densitometry, and bone turnover in 21 early postmenopausal osteoporotic women. Subjects enrolled in the study had a value above the normal average of at least one index of bone turnover: whole body retention (WBR) of 99mTc-methylene-dichloro-bisphosphonate (99mTc-MDP), serum bone gla protein (BGP), urinary hydroxyproline/creatinine excretion (HOP/Cr). After baseline evaluation, patients were randomized for treatment with either sCT (200 IU every other day) or placebo. Treatment with sCT significantly increased VMC by 2.7 +/- 0.9% at 6 months, and 3.3 +/- 0.8% at 1 year, whereas a progressive decline was observed in the placebo group (-2.6 +/- 0.5%, and -3.5 +/- 0.5% after 6 and 12 months, respectively). These changes were associated with a progressive and significant reduction of all parameters of bone turnover in the sCT-treated patients, whereas no changes were detected in the control group during the study period. The differences between the two groups were significant after 1 year for VMC, BGP, and WBR (P less than 0.05, one-way analysis of variance). Thus, 200 IU intranasal sCT administered on alternate days is adequate to stop the fast bone loss occurring early after the menopause in women with high bone turnover rates. This therapeutical modality represents an important addition to the available pharmacologic spectrum for the prevention and treatment of postmenopausal osteoporosis.

Administration, Intranasal↗
PubMed1992

Effect of estrogen and calcitonin on vertebral bone density and vertebral height in osteoporotic women.

Estrogen and calcitonin increase bone density of osteoporotic women, particularly on the axial skeleton. To verify whether the effect of these drugs might in part be biased by spurious increases in bone density due to radiologically irrelevant microfractures, and consequent subtle decreases in vertebral height, we followed the changes in vertebral bone density (VBD), assessed by quantitative computed tomography, in relation to vertebral height (VH) in 60 osteoporotic women. VH was measured as the sum of anterior, central and posterior heights of L1-L3 vertebral bodies on lateral radiographs. Patients received either salmon calcitonin (sCT: 50 IU subcutaneously three times per week, n = 18), hormonal replacement therapy (HRT: conjugated estrogen 0.625 mg/day, days 1-25, plus medroxyprogesterone acetate 10 mg/day, days 16-25 of each month; n = 21) or calcium alone (Ca: 1000 mg/day, n = 21). After 1 year, VBD increased in the HRT group (+5.0 +/- 1.9%, p = 0.010), did not change significantly in the sCT group (+3.3 +/- 2.3%, p = 0.167), and decreased by 6.1 +/- 1.0% (p less than 0.001) in the Ca group. By analysis of variance, the changes induced by HRT and sCT were significantly different from those observed in the Ca group (F = 7.982, p less than 0.001). VH decreased slightly in all three subsets of patients (-0.9 +/- 0.5% in sCT, -1.5 +/- 0.3% in HRT, -0.1 +/- 0.5% in Ca), but these changes were not significantly different between groups (F = 2.545, p = 0.081).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Estrogen status and heredity are major determinants of premenopausal bone mass.

To analyze their relative effects on premenopausal bone mass, we have studied the impact of lifelong estrogen exposure, assessed by an estrogen score (ES; computed on age at menarche, average length of menstrual cycles since menarche, and use of birth control pills), heredity, and some environmental factors on vertebral bone density (VBD), of 63 premenopausal women (age, 19-40 yr). Compared with women with normal bone density (Z score > -1), subjects with low VBD (Z score < -1) had significantly lower ES (15.1 +/- 3.9 vs. 18.7 +/- 2.4, P = 0.001), higher age at menarche (13.8 +/- 1.7 vs. 12.6 +/- 1.4 yr, P = 0.005), and lower serum estradiol (46.9 +/- 37 vs. 86.6 +/- 57 pg/ml, P = 0.023) and estrone levels (107.4 +/- 60 vs. 178.8 +/- 9.0 pg/ml, P = 0.05). Likewise, women in the lowest quartile for VBD had significantly lower ES (15.3 +/- 4.5 vs. 18.1 +/- 2.7, P = 0.006) and higher age at menarche (13.9 +/- 1.9 vs. 12.8 +/- .4, P = 0.02) than those in the upper three quartiles. A higher proportion of subjects with irregular menses (52 vs. 23%, P = 0.03) and a positive family history of osteoporosis (86 vs. 61%, P = 0.04) was found in the low VBD group compared with subjects with normal VBD. VBD correlated positively with ES (r = 0.44, P = < 0.001) and negatively with age at menarche (r = -0.30, P = 0.03) by simple linear regression, whereas no correlation was found between VBD and age, body mass index, parity, lactation, physical activity, sunlight exposure, and dietary calcium and vitamin D intakes. The correlation between VBD and ES improved after correcting for the effect of all the other variables by partial correlation analysis (Pearson partial r = 0.57, P = < 0.01), which also disclosed a significant contribution of dietary calcium to VBD. However, ES was the only significant independent determinant of VBD, by stepwise multiple regression analysis (R2 = 0.24). Therefore, premenopausal estrogen exposure, and possibly genetic predisposition, rather than environmental factors, are the major determinants for the development of peak bone mass before menopause.

Adult↗
PubMed1992

Structure-function relationship of parathyroid hormone: activation of phospholipase-C, protein kinase-A and -C in osteosarcoma cells.

Recent evidence indicates that after PTh interaction with its receptor, both protein kinase-A (PKA) and protein kinase-C (PKC) are activated. To investigate the relationship between PTH structure and protein kinase stimulation, we have analyzed the effects of synthetic PTH fragments on PKA and PKC in the rat osteogenic sarcoma cells, UMR 106-01. Activation of PKA by 10(-7) M bovine (b) PTH-(1-34) was maximal (2.7-fold of control) at 5 min and remained elevated 15 min after hormone exposure. bPTH-(2-34), at equimolar doses, also stimulated PKA, but with a lower potency (1.4-fold of control), whereas propionyl bPTH-(2-34) [pbPTH-(2-34)], bPTH-(3-34), [Tyr34]bPTH-(7-34) amide [bPTH-(7-34)], and bPTH-(30-34) were ineffective. On the other hand, translocation of PKC activity from the cytosol to the membrane after exposure to bPTH-(1-34) was transient, with a peak at 1 min (1.9-fold of control), and returned to basal levels after 5 min. Other fragments, bPTH-(2-34), pbPTH-(2-34), bPTH-(3-34), and bPTH-(7-34), were also active on PKC, with relative potencies of 81%, 67%, 62%, and 51% of bPTH-(1-34), respectively, whereas bPTH-(30-34) was inactive. bPTH-(1-34), bPTH-(2-34), pbPTH-(2-34), and bPTH-(3-34) also induced inositol 1,4,5-trisphosphate production, with a potency order of 1.6-, 1.6-, 1.5-, and 1.6-fold over the control value, respectively, thus indicating activation of phospholipase-C. Neither bPTH-(7-34) nor bPTH-(30-34) caused a statistically significant increase in inositol 1,4,5-trisphosphate production. These results demonstrate that PTH signal transduction through the two different pathways can be dissociated; while activation of the cAMP/PKA system requires amino acids 1 and 2, the phospholipase-C/PKC system is coupled to a longer domain of the hormone's N-terminus.

Animals↗
PubMed1992

Heterogeneous intracellular free calcium responses to parathyroid hormone correlate with morphology and receptor distribution in osteogenic sarcoma cells.

The osteogenic sarcoma cell line UMR 106-01 exhibits heterogeneous morphology and hormone response in subconfluent monolayer cultures. In these studies we have explored the correlation between morphological profiles and patterns of cytosolic calcium [Ca2+]i response to PTH and other agonists in single UMR 106-01 cells loaded with the Ca(2+)-sensitive fluorescent indicator, fura-2. Realtime recording of [Ca2+]i revealed that PTH (10(-7) M) produced a transient [Ca2+]i rise in 19% of the cells studied. [Ca2+]i transients were also induced by prostaglandins E2 and F2 alpha, and fetal bovine serum, but with different response frequencies (20%, 12%, and 58%, respectively). Spatial resolution of changes in [Ca2+]i by video image analysis revealed that the response to PTH was more frequent in large polygonal cells with long cytoplasmic processes and less common in smaller cells growing in clusters, whereas there was no clear subtype specificity for the effects of epidermal growth factor and fetal bovine serum on [Ca2+]i. Autoradiographic analysis of cell monolayers demonstrated a higher density of PTH-binding sites on cells with cytoplasmic extensions, whereas epidermal growth factor-binding sites were largely on colony-forming cells. Thus, the [Ca2+]i response to hormonal stimulation is heterogeneous within UMR 106-01 cell populations and within single cells, and it correlates with receptor density. This suggests that osteoblastic cells respond to PTH by activation of changes in [Ca2+]i only at certain specific steps during osteoblast development or stages of the cell cycle.

Animals↗
PubMed1991

Regulation of skeletal remodeling by parathyroid hormone.

PTH is responsible for the maintenance of calcium homeostasis and normocalcemia. Secretion of PTH is stimulated or suppressed by perturbations in the serum calcium level. The calciotropic effects of PTH are mediated primarily by bone, where PTH-stimulated remodeling may release calcium to the extracellular fluid, and by the kidneys, where calcium reabsorption and phosphate excretion are increased. The effects of PTH in bone are bipolar: including regulation of multiple cell types, especially, both osteoblasts and osteoclasts, and stimulating both bone formation (anabolic effects) and bone resorption (catabolic) effects. The purpose of this review is to discuss the available data regarding PTH-regulated bone remodeling, the role of second messengers produced by polyphosphoinositide hydrolysis, the possible role of G proteins in regulating this reaction, and the biologic effects of activating this system. Greater insight into the complexities of parathyroid hormone-regulated bone remodeling are still required.

Animals↗
PubMed1991

Dissociation of second messenger activation by parathyroid hormone fragments in osteosarcoma cells.

PTH activates multiple second messengers in its target cells, but the level at which the hormonal signal splits into different pathways is still unknown. To achieve insights on this issue, we have studied the structure-function relationship of PTH by analyzing the effects of bovine PTH-(1-34) [bPTH-(1-34)] and PTH fragments truncated at the N-terminus on the intracellular calcium concentration [( Ca2+]i) and cAMP production in the rat osteogenic sarcoma cell line UMR 106-01. [Ca2+]i was measured in single cells using fura-2. When exposed to 10(-7) M bPTH-(1-34), 20% of the cells responded with a transient increase in [Ca2+]i of variable amplitude. Equimolar doses of bPTH-(2-34), propionyl bPTH-(2-34) [(pbPTH-(2-34)], and bPTH-(3-34) also transiently increased [Ca2+]i, whereas both [tyrosine34]bPTH-(7-34) amide [bPTH-(7-34)] and bPTH-(30-34) were ineffective. The amplitude of the [Ca2+] i transients was dose-dependent, with threshold concentrations of 10(-10) M for bPTH-(1-34) and bPTH-(2-34), and 10(-9) M for bPTH-(3-34). The response rate to the active peptides ranged between 10-30%, without a clear dose-relatedness. A second addition of 10(-7) M bPTH-(1-34) to cells prestimulated with equimolar doses of bPTH-(2-34), pbPTH-(2-34), or bPTH-(3-34) produced another transient, whereas after exposure to 10(-7) M bPTH-(1-34), the cells were completely desensitized to a second homologous stimulation, suggesting that the binding affinity of the truncated peptides for the PTH receptor is lower than that of the intact bPTH-(1-34) fragment. In addition, both bPTH-(1-34) and bPTH-(2-34) dose-dependently stimulated cAMP production, but the former was more potent (ED50 = 10(-9) vs. 10(-7) M, respectively). On the contrary, pbPTH-(2-34), bPTH-(3-34), and bPTH-(7-34) had no effect on cAMP. Pretreating the cells with pertussis toxin to enhance cAMP responses via inhibition of Gi potentiated the effect of bPTH-(1-34) and bPTH-(2-34) and disclosed weak but detectable agonist action of pbPTH-(2-34). These results indicate that specific domains of the PTH molecule are linked to activation of different second messenger pathways; while the first two amino acids are indispensable for activating the cAMP system, generation of the [Ca2+]i signal appears to involve a longer domain, including the amino acid residue in position 3.

Animals↗
PubMed1991

Subclinical vitamin D deficiency in postmenopausal women with low vertebral bone mass.

To define the potential role of subclinical vitamin D deficiency in postmenopausal bone loss, we analyzed the levels of circulating 25-hydroxyvitamin D (25OHD) in 539 midwestern caucasian women screened for osteoporosis. Low 25OHD (less than 38 nmol/L) was found in 49 subjects (aged 52-77 yr). Women with low 25OHD had a reduced vertebral bone density (VBD), assessed by quantitative computed tomography, compared to age-matched controls (P less than 0.001). They also had significantly lower levels of serum calcium and phosphate, lower urinary calcium, higher serum alkaline phosphatase, and, in most cases, increased immunoreactive PTH (iPTH) concentrations, suggesting secondary hyperparathyroidism. Furthermore, only in the low 25OHD group did VBD correlate directly with 25OHD (r = 0.41; P less than 0.01), and inversely with iPTH (r = -0.47; P less than 0.01). Multivariate analyses revealed that iPTH was the major determinant of the observed decrease in VBD. Seasonal variations of serum 25OHD were noted only in the control population; in this group the 25OHD levels also correlated with sunlight exposure (r = 0.48; P less than 0.01), as assessed by an outdoor score. Thus, vitamin D deficiency develops when both the endogenous and exogenous sources are insufficient and contributes to a reduced bone mass in elderly women.

Aged↗