Biomedical subjects

C M Gundberg

Publications and source records attributed to C M Gundberg.

At least 19 recordsLinked to original sources

PubMed1995

Vitamin D deficiency in homebound elderly persons.

OBJECTIVE: To assess the vitamin D status in homebound, community-dwelling elderly persons; sunlight-deprived elderly nursing home residents; and healthy, ambulatory elderly persons. DESIGN: A cohort analytic study. PARTICIPANTS: Of 244 subjects at least 65 years old, 116 subjects (85 women and 31 men) had been confined indoors for at least 6 months, either in private dwellings in the community (the Hopkins Elder Housecall Program) or in a teaching nursing home (The Johns Hopkins Geriatrics Center). The 128 control subjects, a healthy ambulatory group, came from the Baltimore Longitudinal Study on Aging. All subjects were free of diseases or medications that might interfere with their vitamin D status. MAIN OUTCOME MEASURES: Serum levels of 25-hydroxyvitamin D (25-OHD) and 1,25-dihydroxyvitamin D (1,25-[OH]2D) were measured in all subjects. In a subgroup of 80 subjects, serum levels of intact parathyroid hormone (PTH), ionized calcium, and osteocalcin and intake of vitamin D (through 3-day food records) were assessed. A randomly selected cohort of sunlight-deprived subjects also had serum levels of vitamin D binding protein measured. RESULTS: In sunlight-deprived subjects overall, the mean 25-OHD level was 30 nmol/L (12 ng/mL) (range, < 10 to 77 nmol/L [< 4 to 31 ng/mL]) and the mean 1,25-(OH)2D level was 52 pmol/L (20 pg/mL) (range, 18 to 122 pmol/L [7 to 47 pg/mL]). In the sunlight-deprived subjects, 54% of community dwellers and 38% of nursing home residents had serum levels of 25-OHD below 25 nmol/L (10 ng/mL) (normal range, 25 to 137 nmol/L [10 to 55 ng/mL]). A significant inverse relationship existed between 25-OHD (ie, Log [25-OHD]) and PTH when they were analyzed together (r = -0.42; R2 = 0.18; P < .001) and for each cohort separately. All other parameters measured, except ionized calcium, differed significantly from the Baltimore Longitudinal Study Group means. The mean (SD) daily intakes of vitamin D (121 [132] IU) and calcium (583 [322] mg) were below the recommended dietary allowance only in the community-dwelling homebound population. The mean vitamin D binding protein level in the sunlight-deprived subgroup was in the normal range. CONCLUSIONS: Despite a relatively high degree of vitamin supplementation in the United States, homebound elderly persons are likely to suffer from vitamin D deficiency.

Aged↗

PubMed1995

A comparison of the effects of parathyroid hormone and parathyroid hormone-related protein on osteocalcin in the rat.

We compared the effects of parathyroid hormone (PTH1-34) and parathyroid hormone-related protein (PTHrp1-34) on osteocalcin release in the isolated rat hindlimb and in intact and thyroparathyroidectomized (TPTX) rats. PTH1-34 suppressed osteocalcin release from perfused rat hindquarters, while PTHrp1-34 had no effect on osteocalcin release, despite comparable stimulation of cAMP production. Similarly, serum osteocalcin declined in the intact and TPTX animals by 5 h after a single dose of PTH1-34, while there was no response to PTHrp1-34. Chronic administration of PTH1-34 or PTHrp1-34 produced comparable hypercalcemia and hypophosphatemia in sham-operated and TPTX animals. Chronic PTH1-34 administration produced significant increases in serum osteocalcin both in the sham-operated rats and in the TPTX animals. However, in animals chronically treated with PTHrp1-34, there was no change at any time point in osteocalcin in either sham-operated or TPTX rats. These differences could be inherent or merely due to potency differences between the two peptides.

Analysis of Variance↗

PubMed1994

The displacement of calcium from osteocalcin at submicromolar concentrations of free lead.

Lead, an environmental toxin, is known to impair some of the functional properties of osteocalcin, a small protein (MW, 5700) active in bone mineralization and resorption. To investigate a possible mechanism of lead toxicity at the molecular level, we have studied the interaction of lead with osteocalcin using 43Ca and 1H NMR. The measured 43Ca NMR linewidth as well as longitudinal relaxation rate (1/T1) of 43CaCl2 progressively increased with increasing amounts of added osteocalcin. A titration measuring 43Ca linewidth as a function of [Ca2+]/[Osteocalcin] ratio could be fitted to a single metal binding site with a dissociation constant of 7 microM. The 43Ca 1/T1 of Ca-osteocalcin decreased in the presence of Pb2+ due to competitive displacement of Ca2+ by Pb2+. The magnitude of decrease in the effect of osteocalcin on 43Ca 1/T1 in the presence of Pb2+ was consistent with the existence of only one tight divalent cation binding site. An analysis of the NMR T1 data in osteocalcin solutions containing both Pb2+ and Ca2+ yielded a Pb-osteocalcin dissociation constant of about 2 nM. The 1H NMR spectra showed Pb-induced changes in the same aliphatic and aromatic resonances of osteocalcin that are also affected by Ca(2+)-binding, supporting interaction of Pb2+ at the Ca2+ site. However, the existence of significant differences between the Pb-osteocalcin and Ca-osteocalcin NMR spectra indicates some differences in the structures of the two complexes. Since Pb2+ inhibits the binding of osteocalcin to hydroxyapatite, the high affinity of Pb2+ for osteocalcin would indicate significant inactivation of osteocalcin even at submicromolar free lead levels. Pb(2+)-induced inactivation of osteocalcin could affect bone mineral dynamics and may be related to the observed inverse correlation between blood Pb(2+)-levels and stature and chest circumference observed in growing children.

Animals↗

PubMed1994

Effects of strength training on bone mineral density: hormonal and bone turnover relationships.

The effects of a 16-wk strength-training program on bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry in 21 men [age 61 +/- 1 (SE) yr]. Sixteen men (age 59 +/- 2 yr) served as control subjects. To investigate the possible hormonal relationships underlying the effects on BMD, serum concentrations of growth hormone, insulin-like growth factor I, and testosterone were determined before and after training. In addition, osteocalcin and skeletal alkaline phosphatase (markers of bone formation) and tartrate-resistant acid phosphatase (a marker of bone resorption) were measured before and after training to assess bone turnover. The training program resulted in a 2.8 +/- 0.6% increase in femoral neck BMD (1.004 +/- 0.037 vs. 1.031 +/- 0.037 g/cm2; P < 0.001). However, there were no significant changes in total body, anterioposterior spine, lateral spine, Ward's triangle, or greater trochanter BMD. Moreover, there were no significant changes in growth hormone, insulin-like growth factor I, testosterone, osteocalcin, or skeletal alkaline phosphatase. There were no changes in the control group. Thus, strength training can increase femoral neck BMD, and this effect does not appear to be accompanied by changes in anabolic hormones or markers of bone formation and resorption.

Absorptiometry, Photon↗

PubMed1994

Racial differences in parathyroid hormone dynamics.

Elevations in PTH levels have been reported in black subjects. Such observations have not been consistent, however, and seem paradoxical in view of the known bone-resorptive action of this hormone and the fact that black subjects have a higher bone mineral density and fewer fractures than their white counterparts. In this study, we used dynamic stimulation of the calcium-PTH axis to fully characterize potential racial differences in PTH dynamics. We, therefore, defined the inverse sigmoidal curve that describes the relationship between serum ionized calcium concentration and intact PTH levels in six normal white and six normal black volunteers and determined the four parameters that characterize this relationship. An elevation in any one of these parameters can result in hyperparathyroidism. Black subjects had higher maximal and minimal PTH responses to hypo- and hypercalcemia (mean intact PTH levels of 9.2 +/- 13 and 0.7 +/- 0.1 pmol/L respectively) than white subjects (6.9 +/- 0.6 and 0.3 +/- 0.1 pmol/L, respectively). There were no differences in the set-points or slopes of the curves. Despite the higher baseline and stimulated endogenous PTH levels in black subjects, their baseline and stimulated osteocalcin levels were lower. Our dynamic studies, therefore, document mild hyperparathyroidism in black subjects and suggest mild skeletal resistance to PTH.

Adult↗

PubMed1993

Effects of aluminum on rat bone cell populations.

Aluminum (Al) loading is associated with reduced bone formation and osteomalacia in human and certain animal models. However, uncertainty exists as to the cellular effect(s) of Al as both inhibition and stimulation of osteoblast proliferation have been reported. Furthermore, the extent to which Al affects osteoprogenitor cell populations is unknown. To determine the cellular effects of Al in the rat, an animal model in which Al bone disease has been produced, we compared the in vitro effect of 10-50 microns Al on the proliferation and hydroxyproline collagen formation of marrow osteoprogenitor stromal cell populations and perinatal rat calvarial osteoblasts. In subconfluent cultures, Al suppressed proliferation of both marrow fibroblast-like stromal cells and calvarial osteoblasts. In confluent cultures, however, Al selectively stimulated periosteal fibroblast and osteoblast DNA synthesis and collagen (hydroxyproline) production, both in the presence or absence of 1,25-dihydroxyvitamin D. Osteocalcin was not detected in osteoblast-conditioned media or extracellular matrix. These observations suggest that the bone formation defect associated with Al toxicity in growing rats may be a function of impaired patterns of osteoprogenitor/osteoblast proliferation. Furthermore, the Al-stimulated increase in collagen formation is consistent with the development of osteomalacia in Al-toxic humans and animals. The mechanism by which Al stimulated DNA synthesis and collagen production in more mature cultures awaits further study.

Aluminum↗

PubMed1993

Strength training increases regional bone mineral density and bone remodeling in middle-aged and older men.

To determine the effects of strength training (ST) on bone mineral density (BMD) and bone remodeling, 18 previously inactive untrained males [mean age 59 +/- 2 (SE) yr] were studied before and after 16 wk of either ST (n = 11) or no exercise (inactive controls; n = 7). Total, spinal (L2-L4), and femoral neck BMD were measured in nine training and seven control subjects before and after the experimental period. Serum concentrations of osteocalcin, skeletal alkaline phosphatase isoenzyme, and tartrate-resistant acid phosphatase were measured before, during, and after the experimental program in all subjects. Training increased muscular strength by an average of 45 +/- 3% (P < 0.001) on a three-repetition maximum test and by 32 +/- 4% (P < 0.001) on an isokinetic test of the knee extensors performed at 60 degrees/s. BMD increased in the femoral neck by 3.8 +/- 1.0% (0.900 +/- 0.05 vs. 0.933 +/- 0.05 g/cm2, P < 0.05) and in the lumbar spine by 2.0 +/- 0.9% (1.180 +/- 0.06 vs. 1.203 +/- 0.06 g/cm2, P < 0.05). However, changes in lumbar spine BMD were not significantly different from those in the control group. There was no significant change in total body BMD. Osteocalcin increased by 19 +/- 6% after 12 wk of training (P < 0.05) and remained significantly elevated after 16 wk of training (P < 0.05). There was a 26 +/- 11% increase in skeletal alkaline phosphatase isoenzyme levels (P < 0.05) after 16 wk of training.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗

PubMed1993

The calciotropic hormone response to changes in serum calcium during exercise in female long distance runners.

The purpose of this study was to evaluate the effects of 45 min of submaximal running on calciotropic hormone levels in female long distance runners. Fourteen long distance runners and six sedentary controls (less than three exercise sessions per week) had bone mineral density (BMD) of the lumbar spine (L2-L4), femoral neck, and tibia measured by dual photon absorptiometry. All of the sedentary controls and eight runners (NormR) had BMD values within the normal range for women of their age. The remaining six runners had BMD L2-L4 measures greater than 1 SD below normal values and were classified as the low bone density group (LowR). Subjects were tested for their calciotropic hormone response to submaximal running using both an oral calcium load (dairy product), to induce a significant elevation in serum calcium, and no calcium load. In both exercise tests, serum calcium rose in NormR and LowR, with a greater increase induced by the oral calcium load. In NormR, the increase in serum calcium resulted in decreased PTH levels, with small increases in calcitonin levels. In contrast, LowR showed significant (P < 0.05) increases in PTH levels, with concurrent decreases in calcitonin levels. The changes in calciotropic hormone levels were shown to be significantly associated with BMD. Our results suggest that in well trained female runners with low spinal bone density, long distance running may aggravate this condition through the effect of exercise-related elevations of PTH on bone turnover. Alterations in the homeostatic control mechanisms for calcium during exercise should also be considered in the clinical assessment of female runners with spinal osteopenia.

Adult↗

PubMed1992

The osteocalcin propeptide is not secreted in vivo or in vitro.

Osteocalcin is initially synthesized as an 11 kD molecule consisting of a 23-residue translocation signal peptide that is cleaved during translation, a 26-residue propeptide that targets the protein for gamma-carboxylation, and the 49-residue mature protein. Although the majority of newly synthesized osteocalcin is deposited into bone matrix, a small amount can be detected in blood, and it is this characteristic that has led to its current clinical use as a specific index of osteoblastic activity. Nothing is known, however, about the fate of the propeptide. If osteocalcin and the propeptide are cosecreted, then the concentration of the propeptide could also be useful as a marker of osteoblastic function and, further, may be superior to osteocalcin because it would be unaffected by binding to bone. To test this hypothesis, we synthesized a peptide corresponding to 21 residues of the osteocalcin propeptide from humans and produced a polyclonal antibody to this peptide. Human sera were screened for the presence of the propeptide, and the human osteosarcoma cell line MG-63 was tested for secretion of the propeptide. We could not detect any osteocalcin propeptide in sera from normal adults or individuals with renal failure or primary hyperparathyroidism or those on long-term coumadin therapy. Likewise there was no propeptide present in media from cells grown in the presence of vitamin K, 1,25-(OH)2D3, warfarin, or warfarin plus 1,25-(OH)2D3. In contrast, the cell extract, characterized by high-performance liquid chromatography, contained mature osteocalcin, free propeptide, and the proosteocalcin precursor when cells were grown in the presence of 1,25-(OH)2D3 alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcitriol↗

PubMed1992

Biochemical parameters associated with low bone density in healthy men and women.

A causal role in age-related bone loss has been attributed to alterations in vitamin D status, the bone mineral regulating hormones, and/or renal function. We assessed biochemical parameters of bone metabolism and renal function in healthy subsets of young and old men (n = 191) and women (n = 120) and evaluated the relationships between these parameters and bone mineral density (BMD) in the radius, spine, and femur. There were no significant associations between BMD at any site and serum 25-OHD, 1,25-(OH)2D, PTH, or creatinine clearance in either young men or in young or old women, after controlling for age. In old men, however, lower radius BMD was significantly related to higher PTH and higher 1,25-(OH)2D and marginally related to lower 25-OHD values. In young men, there were unexpected but significant associations between lower femoral neck BMD and higher serum osteocalcin and urinary calcium/creatinine excretion after age adjustment. In old women, lower spine and radius BMD was also significantly correlated with higher serum osteocalcin. In this healthy, vitamin D-replete population, there were significant cross-sectional declines in BMD in the femur in young and old men and at all sites in old women. Elevated remodeling may be an important feature that contributes to reduced femoral BMD in young men and reduced spine and radius BMD in old women. However, compromised renal function or levels of 1,25-(OH)2D or elevated PTH appear to be neither necessary nor relevant as determinants of osteopenia in the spine or femur in these normal, healthy men and women.

Adult↗

PubMed1992

Osteocalcin and its message: relationship to bone histology in magnesium-deprived rats.

These studies examine effects of brief Mg deprivation on bone histomorphometry and on secretion and synthesis of the specific osteoblast product, osteocalcin. Osteocalcin mRNA was determined in calvaria-derived cells and was correlated to circulating concentrations of the protein after 8 days of Mg deprivation. Circulating osteocalcin was decreased in Mg-deprived rats when compared with pair-fed normal rats after 8 days of Mg deprivation, with no significant changes in calcium or 1,25-dihydroxyvitamin D [1,25(OH)2D]. Serial sampling demonstrated a difference in osteocalcin levels by 2 days of Mg deprivation, before any changes in circulating calcium or parathyroid hormone were present. Although circulating osteocalcin is decreased in Mg-deprived animals, levels can be stimulated with 1,25(OH)2D3. Osteocalcin mRNA is reduced after Mg deprivation, suggesting that low circulating levels are due, at least in part, to reduced osteocalcin synthesis. Mg-deprived rats had diminished bone volume and abnormal histological features consistent with disorganized and chaotic bone remodeling. These findings indicate that low-Mg intake during growth can alter the quality and quantity of bone and suggest that Mg deprivation may contribute to the development of osteoporosis.

Animals↗

PubMed1992

Development and validation of a radioimmunoassay for mouse osteocalcin: paradoxical response in the Hyp mouse.

The hypophosphatemic (Hyp) mouse is a model for human familial hypophosphatemic rickets. To test the hypothesis that there is an osteoblastic defect in these animals, serum osteocalcin levels were measured in Hyp mice and their normal littermates. Furthermore, the effects of phosphorus deprivation, phosphorus loading, and 1,25-dihydroxyvitamin D3 administration on serum osteocalcin levels were examined. Osteocalcin was purified from mouse hindlimbs, and a polyclonal antibody to this material was produced in a goat. The antibody recognized native and decarboxylated mouse osteocalcin, but could not recognize osteocalcin from several other species. A RIA was developed which had a minimal detection limit of 0.4 nmol/liter (2.2 micrograms/liter) and half-maximal displacement at 2.7-3.3 nmol/liter (14.8-18.2 micrograms/liter). The intraassay coefficient of variation was 6.4%, while the interassay coefficient of variation was 12%. Dilutions of mouse serum samples varied by less than 15%. Analytical recovery was typically greater than 90%. Serum osteocalcin concentrations in Hyp and normal mice were shown to decrease with age. However, circulating osteocalcin levels in Hyp mice were higher than those in their normal littermates regardless of the age of the animal (P less than 0.001). One week of a high phosphorus diet resulted in an increase in serum phosphate in normal and Hyp mice, but serum osteocalcin concentrations were unaffected. On the other hand, dietary phosphorus deprivation for 4 weeks resulted in comparable hypophosphatemia in both Hyp and normal mice, and serum osteocalcin increased in both groups of animals. Intraperitoneal injection of 30 ng/day 1,25-dihydroxyvitamin D3 for 7 days resulted in a 215 +/- 33% increase in serum osteocalcin in normal animals, while the same regimen produced a 250 +/- 29% decrease in the Hyp mouse. Our results are consistent with the hypothesis that abnormal osteoblastic activity is present in Hyp mice. Furthermore, hypophosphatemia may be a general regulator of osteocalcin synthesis or secretion in the mouse.

Animals↗

PubMed1991

The influence of ibuprofen on fracture repair: biomechanical, biochemical, histologic, and histomorphometric parameters in rats.

Ibuprofen is a widely used cyclo-oxygenase inhibitor in clinical practice. It has been demonstrated by others to have an inhibitory effect on fracture repair in animals. In the present study, we were unable to demonstrate any significant alterations in fracture biomechanics as measured by torsion testing and fracture stage in mature Sprague-Dawley rats treated with 30 mg/kg/day oral dose of ibuprofen, starting 3 days following fracture, over a 12-week time interval. Fracture histology and serum osteocalcin levels were no different in treated animals than control animals. Furthermore, histomorphometric parameters of bone remodeling, including bone volume and bone formation rate in the intact tail vertebrae of these animals with unilateral femur fractures, were no different between treated and control animals.

Animals↗

PubMed1991

Partial characterization of rat marrow stromal cells.

Fibroblast-like rat marrow stromal cell (CFU-F) cultures have been characterized in terms of their responsiveness to calciotropic hormones, metal ions, the nonsteroidal antiinflammatory drug, and by their putative paracrine role in the maintenance of active populations of osteoblasts at the marrow-bone interface. These studies indicate that CFU-Fs lack a complete osteoblast signature. Subconfluent CFU-Fs grown in the presence or absence of 10(-7) M dexamethasone lack receptors for PTH and calcitonin, and fail to show enhanced cAMP or cGMP responses to 10(-7) M 1-34 PTH (rat), or any evidence of osteocalcin production [+/- 10(-9) M 1,25-(OH)2D3]. Low concentrations of fluoride [10(-12) and 10(-9) M] stimulated CFU-F grown in vitro in serum-free media, though higher levels (10(-7) and 10(-6) M), inhibited growth in vivo and in vitro. Aluminum (10(-12)-10(-7) M) and ibuprofen (10(-7) M) did not alter normal growth patterns, indicating an action on bone cells more differentiated than CFU-Fs. Serum-free conditioned medium (CM) from control and ovariectomized (OVX)/OVX+ dihydrotachysterol-Rx rat CFU-F cultures was mitogenic for neonatal rat calvarial osteoblasts in vitro, but not for ROS 17/2.8 cells. The studies affirm the mesenchymal-like character of CFU-Fs and project their significant role in sustaining functional endosteal osteogenic cell populations.

Animals↗

PubMed1991

Homologous amino-terminal radioimmunoassay for rat parathyroid hormone.

Existing radioimmunoassays for parathyroid hormone (PTH) in rat plasma are based on cross-reactivity of rat PTH (rPTH) with heterologous antisera. We used the synthetic NH2-terminal fragment of rPTH [rPTH-(1-34)] to develop a homologous radioimmunoassay for circulating PTH. An antiserum to rPTH-(1-34) was raised in a goat (G-813), and the same peptide was used as radioligand (125I) and standard. Purification of the label by high-performance liquid chromatography (HPLC) increased specific binding greater than twofold and sensitivity by 50-100%. With a final antiserum dilution of 1:70,000, maximum specific binding of 30-33%, nonspecific binding of 1-5%, and 50-microliters sample additions, the assay detection limit was 1.8-2.5 pmol/l. A midregional fragment of human PTH did not displace 125I-labeled rPTH-(1-34). HPLC of extracts of rat parathyroid glands and hyperparathyroid plasma showed only a single peak of immunoreactivity that eluted 2 min after rPTH-(1-34). Dose dilution curves for rat parathyroid gland extracts, rPTH-(1-34) added to rat plasma, and endogenous rat plasma PTH all paralleled the standard curve. Immunoreactive PTH (irPTH) was detectable in greater than 90% of fasting normal rat plasma and changed appropriately in response to hyper- and hypocalcemia induced by low-calcium and vitamin D-deficient diets, injections of calcium and EDTA, and after thyroparathyroidectomy. The normal range for rat plasma irPTH was less than 2.0-12 pmol/l, in general agreement with bioassay results of others. Thus rPTH-(1-34) is an excellent immunogen for raising antisera to rPTH, and assays incorporating it may be of great value in studying rat parathyroid physiology.

Animals↗

PubMed1991

Acute changes in serum osteocalcin during induced hypocalcemia in humans.

Although levels of serum osteocalcin are thought to be an indicator of osteoblastic activity and bone formation, there is little information regarding the acute effects of changes in calcium or PTH levels on circulating osteocalcin concentrations. To study the effect of stepwise decreases in ionized calcium (CaI) on osteocalcin levels, we infused six normal subjects with citrate for four 30-min intervals using two different protocols. One protocol (pulse infusion) used alternating rates of infusion and resulted in rapid stepwise decrements in serum CaI. The second protocol (continuous infusion) used constant intermediate rates of citrate infusion and produced slower decrements in CaI, but with similar changes in magnitude. We monitored serum CaI, intact PTH, and osteocalcin concentrations during the course of these infusions. During each step of the pulse infusion the osteocalcin responses to changes in CaI in general were parallel to the changes in PTH (r = 0.462; P = 0.02) and were inversely correlated to CaI (r = -0.562; P = 0.003). The osteocalcin concentrations at the end of each 30-min period were higher than at the beginning of that period; over the total 120 min, osteocalcin levels rose from 3.46 +/- 0.63 to 6.88 +/- 1.08 micrograms/L (P less than 0.05). In contrast, during the first two periods of the continuous infusion, osteocalcin concentrations changed slightly. Only during the last two periods of the continuous infusion did osteocalcin respond in a manner characteristic of that observed with the pulse infusion. These data indicate that osteocalcin concentrations in the circulation may be acutely regulated by calcium and/or PTH.

Adult↗

PubMed1991

Parameters of calcium metabolism during a pilot study of cyclosporin A in patients with symptomatic primary biliary cirrhosis.

Twelve patients with serologically and histologically defined symptomatic primary biliary cirrhosis were randomized to receive either oral cyclosporin A or vehicle placebo. The cyclosporin A-treated group had improvement in serum alkaline phosphatase and gamma-glutamyltransferase, suggesting a moderating effect on the course of the liver disease. However, other indices of the liver disease, including liver biopsies, did not show significant improvement. The purpose of this study was to examine the effect of the cyclosporin A treatment on serum indicators of bone and mineral metabolism in these patients, as in its later stages, primary biliary cirrhosis is associated with significant osteopenic bone disease. There were no significant changes in serum calcium, phosphate, magnesium, or vitamin D metabolites between the two groups. However, after one year of treatment, mean serum parathyroid hormone level was significantly lower in the cyclosporin A treatment group, and serum osteocalcin rose significantly. There were no significant changes in any parameter of mineral metabolism in the placebo group. The changes in parathyroid hormone and osteocalcin following cyclosporin A therapy suggest a reduction in the secondary hyperparathyroidism commonly seen with primary biliary cirrhosis and also an increase in bone formation, respectively. This study therefore provides preliminary evidence that cyclosporin A therapy seems to have a mild beneficial effect on the abnormalities of mineral metabolism seen with this disorder.

Bone Diseases, Metabolic↗

PubMed1990

Skeletal effects of sodium fluoride during hypokinesia.

This study tested the capacity of fluoride (F) to prevent the disuse-associated reduction in bone formation/growth. Suspending young male Wistar rats by the tail for 2-2.5 weeks reduced femoral cortical (P less than 0.05) and trabecular (P less than 0.01) bone areas. Tetracycline labelling showed that the decrement in cortical area was largely due to a reduction in the percent periosteal mineralizing surface (PsMS). Periosteal mineral apposition rate (PsMAR) was not affected. Endosteal mineralizing surface (EsMS) and mineral apposition rate (EsMAR) were significantly stimulated spontaneously during the second week of suspension. F treatment (5 mg/kg/day i.p.) prevented the loss in bone area, and established a trend toward increased PsMS without affecting EsMS and EsMAR. None of these changes are associated with alterations in serum Ca, P or osteocalcin. F treatment in hypokinetic animals caused a decrease in serum PTH (-21% compared to control; P = 0.001). We conclude that F prevents the development of hypokinetic osteopenia in rats.

Animals↗