Biomedical subjects

W J Visser

Publications and source records attributed to W J Visser.

At least 19 recordsLinked to original sources

PubMed1994

Brittle bones in spontaneously diabetic female rats cannot be predicted by bone mineral measurements: studies in diabetic and ovariectomized rats.

Spontaneously diabetic BB rats were sham operated (SO) or ovariectomized (OVX) within days after onset and studied after 4, 8, and 12 weeks. Analyses included histomorphometry of proximal tibial metaphyses, biochemical analyses of humeri, DXA analyses, and biomechanical testing of femora. In SO diabetic rats, no osteoblasts, osteoid tissue, or osteoclasts were present on the trabecular bone surface, but trabecular bone volume (TBV) remained normal compared with control BB rats. The concentration of IGF-I per dry weight of humerus was decreased after 12 weeks of diabetes, whereas the concentrations of calcium and osteocalcin did not change. DXA analysis showed normal bone mineral density (BMD) at both diaphyseal and metaphyseal femoral areas. On biomechanical testing, angular deformation, energy absorption, and torsional strength of the femora were decreased after 8-12 weeks of diabetes, but stiffness was normal. Ovariectomy in diabetic rats caused a decrease in femoral BMD especially at the metaphysis, and there was a trend toward decreased TBV in the tibial metaphysis; TBV loss was less marked than in control OVX rats, however. The increase in BMD at the femoral diaphysis, measured after 12 weeks of OVX in control rats, was absent in diabetic rats. Multiple-regression analysis indicated that the presence of diabetes but not ovariectomy, weight, and mineral content correlated with decreased energy absorption, angular deformation, and strength of the femora. The data infer that the (near) absence of unmineralized bone matrix in severely diabetic rats alters bone microarchitecture and ultimately results in brittle bones, which is not predicted by BMC or BMD measurements.

Absorptiometry, Photon↗

PubMed1994

Lysosomal storage diseases: cellular pathology, clinical and genetic heterogeneity, therapy.

Lysosomal storage diseases are genetically determined metabolic diseases characterized by dysmorphology and dysfunction of the lysosomal system. The lysosomal pathology can have different causes; these are (i) the deficiency of a lysosomal enzyme or subunit thereof, (ii) the deficiency of a protein assisting one or more lysosomal enzymes in their catalytic function by activation and/or stabilization, or by substrate presentation, (iii) the deficiency or dysfunction of a lysosomal membrane carrier protein essential for the export of degradation products from the lysosomal interior to the cytoplasm or, (iiii) defective targeting of lysosomal proteins to the lysosomes. This excerpt of an oral presentation given at Eurolab 93 starts with a general introduction on lysosomes and lysosomal storage diseases and devotes attention to current issues in this field.

Humans↗

PubMed1992

Bone and mineral metabolism in the adult guinea pig: long-term effects of estrogen and androgen deficiency.

The effects of androgen and estrogen deficiency on skeletal homeostasis were studied in the guinea pig. Male and female adult (7 months old) guinea pigs were either sham operated (9 females and 7 males) or gonadectomized [9 ovariectomized (OVX) females and 6 orchidectomized (ORX) males] and sacrificed 4 months later for evaluation of bone mass, bone turnover, and serum calcium homeostasis. Parameters of bone turnover, calcium homeostasis, and vitamin D metabolites were similar in all groups except for increased serum IGF-I concentrations (+30%) in males compared to females. Gonadectomy resulted in a 50% decrease in serum IGF-I concentrations in males only (p < 0.001). Volume, total calcium content, and cortical density of the tibia were significant higher in males than in females. Estrogen deficiency had no effect on bone volume or calcium content. Androgen deficiency resulted in a significant lower volume and calcium content of the tibia and in a lower calcium content of the distal lumbar vertebrae. Single-photon absorptiometry of the tibia showed that only cortical, not trabecular bone density of the tibia was decreased after ORX. Histomorphometric studies of the tibial metaphysis also did not show significant differences in trabecular bone volume between sham-operated and ORX males. We conclude that in adult male guinea pigs androgen deficiency results in a decrease in (cortical) bone volume and content concomitant with decreased IGF-I levels. In female guinea pigs of the same age, estrogen deficiency did not affect total or regional bone mass.

Absorptiometry, Photon↗

PubMed1992

The midgestational human fetal pancreas contains cells coexpressing islet hormones.

In the fetal development of the mouse pancreas, endocrine cells have been found that express more than one hormone simultaneously. Our objective was to evaluate the existence of such cells in the human fetal pancreas. We found cells coexpressing two of the major pancreatic hormones (insulin, glucagon, and somatostatin) in sections of eight midgestational (12-18 weeks) pancreata and in 0-7% of cells in single-cell suspensions from midgestational pancreata. By electron microscopy, using granule morphology and immunoelectron microscopic techniques, we could confirm these findings and even detect cells containing three hormones. Morphologically different granules contained different immunoreactivities, suggesting parallel regulation of hormone production and packaging. In six newborn pancreata (born after 22-40 weeks of gestation), we could not find any multiple-hormone-containing cells. Subsequently, we evaluated whether multiple-hormone-containing cells proliferate by using pancreatic fragments and single-cell preparations at the light and electron microscopic level (six pancreata). No endocrine hormone-containing cells incorporated bromodeoxyuridine during a 1-hr culture period, indicating that these cells have lost the ability to proliferate under the conditions chosen. We conclude that, as in mice, the human fetal pancreas of 12-18 weeks of gestation contains endocrine cells that express multiple hormones simultaneously. These (multiple) hormone-containing cells do not seem to proliferate under basal conditions.

Bromodeoxyuridine↗

PubMed1992

Bone and mineral metabolism in aged male rats: short and long term effects of androgen deficiency.

Both short and long term effects of androgen deficiency and steroid replacement therapy on skeletal homeostasis were investigated in aged (13-month-old) male rats. The animals were either sham operated (n = 28) or orchidectomized (orch; n = 89). The orch animals were divided into 5 groups; 26 rats received an empty sc Silastic implant (orch), all others received an implant containing testosterone (T), 5 alpha-dihydrotestosterone (DHT), 17 beta-estradiol (E2), or nandrolone (Nandro; 15-16 rats in each group). Half of the rats were killed 1 month (short term experiment) after implantation; the others were killed 4 months after implantation (long term experiment). Short term androgen deficiency caused a significant increase in both serum osteocalcin and histomorphometric parameters of bone turnover measured at the proximal tibial metaphysis, but not in a significant decrease in bone mass at this site. This increase in bone turnover was prevented not only by T and DHT, but also by E2 and Nandro. Long term androgen deficiency resulted in a decrease in the calcium content of both tibia and lumbar vertebrae. Cancellous bone volume in the proximal tibial metaphysis was +/- 50% lower in the orch group (P less than 0.001) 4 months after orchidectomy. At the same time, cortical bone was lost in orch rats; femoral cortical thickness was reduced by 12% (P less than 0.01), and cortical density tended to be lower. T, DHT, E2, or Nandro treatment completely prevented this decrease in cortical thickness and density. T and Nandro were also able to prevent the cancellous bone loss. DHT could only partly prevent cancellous bone loss. E2 treatment resulted not only in a sustained decrease in both serum osteocalcin concentrations and histomorphometric indices of bone turnover, but also in a net gain of cancellous bone volume (P less than 0.05 vs. sham). No significant differences in serum concentrations of vitamin D metabolites or nephrogenous cAMP were observed between groups in both short and long term experiments. We conclude that bone mass in aged male rats was significantly decreased 4 months after orchidectomy, preceded by an early increase in bone turnover. Both the early increase in bone turnover and the later decrease in bone mass were prevented by aromatizable and nonaromatizable androgens by estrogen and by nandralone.

Aging↗

PubMed1992

The effects of systemic insulin, insulin-like growth factor-I and growth hormone on bone growth and turnover in spontaneously diabetic BB rats.

Spontaneously diabetic BB rats have a markedly depressed longitudinal bone growth and bone formation/turnover. In this study, male diabetic BB rats were infused intraperitoneally or subcutaneously for 2 weeks with hormones that are believed to stimulate skeletal growth and/or trabecular bone formation: insulin (3 or 4 U/day), human GH (hGH; 400 mU/day), recombinant human insulin-like growth factor-I (rhIGF-I; 300 or 600 micrograms/day) and testosterone (80 micrograms/100 g body weight per day). Saline-treated diabetic BB rats had decreased plasma concentrations of IGF-I and osteocalcin (OC) (OC, 3.7 +/- 0.3 vs 13.1 +/- 0.8 (S.E.M.) nmol/l in controls); bone histomorphometry showed decreased epiphyseal width, osteoblast surface (0.04 +/- 0.04 vs 1.5 +/- 0.3%) and osteoid surface, and mineral apposition rate (MAR) (1.8 +/- 0.5 vs 7.9 +/- 0.6 microns/day). Testosterone and hGH infusions had no effect on weight loss or on decreased skeletal growth and bone formation of diabetic rats, nor did they increase plasma IGF-I concentrations. Insulin infusions into diabetic rats resulted in hyperinsulinaemia and accelerated weight gain. The epiphyseal width, osteoblast/osteoid surfaces and OC levels of insulin-treated rats were normalized or stimulated well above control values (osteoblast surface, 4.3 +/- 0.8%; plasma OC, 16.1 +/- 1.4 nmol/l); the MAR (4.0 +/- 0.9 microns/day) was only partly corrected after the 2-week infusion. Infusions of rhIGF-I into diabetic rats doubled but did not restore plasma IGF-I levels to normal; weight gain, however, was similar to that in control rats. IGF-I treatment had no effect on epiphyseal width, osteoblast/osteoid surfaces and OC concentrations, but improved the decreased MAR (4.6 +/- 1.2 microns/day).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

A comparative investigation on autologous mandibular and iliac crest bone grafts. An experimental study in sheep.

Nine Friesian sheep (age 1.5-2 years) were used to evaluate the quality of bone repair in artificial cleft-like maxillary defects repaired with autologous bone grafts of embryologically different origin. After bilateral extraction of the upper first deciduous molar the tooth socket was enlarged resulting in an open connection between the oral and nasal cavities. In the same session a graft, obtained from the iliac crest, was implanted in one of the two bilateral maxillary defects and on the opposite side a graft, obtained from the mandible, was inserted. During the experiment, serial radiographs were taken. After six months the sheep were sacrificed and the bone of the grafted areas was submitted to histological and histomorphometric investigation. Comparing both areas, it appeared that the quality of bone remodelling and alveolar reconstruction was independent of the origin of the grafts.

Alveolar Process↗

PubMed1991

Bone growth and remodeling after distraction epiphysiolysis of the proximal tibia of the rabbit. Effect of electromagnetic stimulation.

The effect of pulsed electromagnetic stimulation on bone formation was tested in a lower-limb-lengthening model in the rabbit. Limb lengthening was performed by distraction epiphysiolysis. A specially designed external distraction device allowed 10 mm of lengthening of the tibia. Coils to generate a pulsed electromagnetic field were clipped onto the distractor. Stimulation started after a distraction period of three weeks and was continuous for 18 weeks. A control group received the same treatment without stimulation. Bone formation in the elongated zone was evaluated by computed tomography, scintigraphy, and histology. Bone healing involved accretion of callus followed by a process of remodeling, resulting in the formation of a solid cortex. The formation of a diaphysislike structure at the original site of the metaphysis progressed from the distal end of the elongated zone upward. Electromagnetic stimulation had no effect on the rate or extent of bone formation and remodeling.

Animals↗

PubMed1990

Effect of direct current stimulation on bone growth after distraction epiphysiolysis of the rabbit tibia.

The effect of direct current stimulation on bone formation during limb lengthening was tested in a lower leg lengthening model in the rabbit. Limb lengthening was performed by distraction epiphysiolysis. A specially designed external distraction device was placed at the tibia. The distractor allowed 10 mm of lengthening in 4 weeks. Two weeks after starting the distraction, a platinum electrode was passed through the anterior cortex below the tibial tuberosity and advanced via the medullary cavity so that the tip rested in the elongated zone. Stimulation started at the time of placement of the electrodes and was continued for 3 weeks. The electrode in the elongated zone served as the cathode; the anode was placed subcutaneously. A 20 microA stimulus was selected. A control group received the same treatment without stimulation. Bone formation in the elongated zone was evaluated by histology and scintigraphy. The data from this experiment show that direct current stimulation in the early phase of a limb lengthening procedure had no effect on the extent of bone formation in the elongated zone.

Animals↗

PubMed1990

The value of local 99mTc(Sn)-MDP bone to soft tissue uptake ratio in osteoporosis, before and during fluoride therapy.

The reproducibility and diagnostic value of local bone to soft tissue uptake ratio of 99mTc(Sn)-MDP as a bone tracer was examined in a prospective study in 35 patients who were under investigation and/or treatment for postmenopausal osteoporosis. The ratio of tracer uptake in the second lumbar vertebra (L2) and both femoral shafts was calculated from the number of counts in suitable regions of interest. Results obtained with settings and calculations in the routine practice were compared to the results obtained by revision of all raw data in one run by one person. The results were compared to the serum alkaline phosphatase activity (AP) and to local bone mineral mass as determined by dual photon absorptiometry (DPA). In 15 patients serial measurements during fluoride therapy were also compared to serum osteocalcin values and to bone histomorphometric data. The precision error of the calculation of uptake ratios from raw counts (including selection of region of interest) was 13.9% for the femoral shaft and 14.7% for L2. The mean difference between left and right femoral shaft in individuals was not significant and its variance was small P greater than 0.1). There was a weak but significant linear correlation between local uptake ratio in the spine and AP in the total material (r = 0.328 P less than 0.01). However, changes in local uptake ratio during therapy with fluoride in 15 patients were too small to be of any value and did not correlate with changes in alkaline phosphatase or osteocalcin or trabecular surface covered with osteoblasts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Arterial stenting with self-expandable and balloon-expandable endoprostheses.

Coronary angioplasty is complicated by acute occlusion (within 24 hours) and late restenosis (within 6 months) in 2-5% and 20-40% of the cases, respectively. Vascular endoprostheses (stents) may provide the cardiologist with a solution to some of these complications. Several stent-devices are now available for experimental and clinical evaluation. In this study we describe our experience with two metallic stents in normal arteries of swine. Self-expandable, stainless steel stents (3.5 mm diameter) were implanted in 17 peripheral arteries, eight of which were deendothelialized by prior balloon angioplasty. Following implantation, the animals received antithrombotic therapy with acenocoumarol and aspirin (8 stents), or aspirin alone (9 stents). After 1 week repeat angiography was performed, which showed patency of all stented arteries. Microscopy showed complete covering by neointima, 80 microns in thickness. This self-expandable stent (SES) and a balloon-expandable stent (BES), constructed of tantalum, were implanted in normal coronary arteries. SES (3.0 and 3.5 mm) receiving animals were treated with coumadines (10 stents) or received no antithrombotic treatment (16 stents) after implantation. BES receiving animals were also not treated (10 stents). Three untreated animals with SES died suddenly within 48 hours. Postmortem examination showed partial or complete thrombosis of all six stents in these animals, resulting in a patency rate of 62% after 1 week. All animals with SES, which were treated with coumadines, and all animals with BES (untreated) had patent stents after one week. It is concluded that SES implanted in normal coronary arteries of pigs, which do not receive additional antithrombotic treatment, show a 38% occlusion rate within 48 hours, but show 100% patency after 1 week, when the animals are treated with coumadines. BES implanted in normal coronary arteries of pigs, which do not receive antithrombotic drugs, are 100% patent after 1 week.

Angioplasty, Balloon, Coronary↗

PubMed1990

No effect of APD (amino hydroxypropylidene bisphosphonate) on hypercalcemia in patients with renal osteodystrophy.

Hypercalcemia, due to autonomous functioning of the parathyroids following long standing secondary hyperparathyroidism, is a well known complication in patients with renal osteodystrophy, which can on most cases be treated by parathyroidectomy only. While patients with renal osteodystrophy react favorably to supplementation of active vitamin D metabolites to prevent or reverse renal osteodystrophy, the use of these drugs is bound to result in greater hypercalcemia in those patients who are already hypercalcemic. The question rose if the bisphosphonate amino hydroxypropylidene bisphosphonate (APD) would decrease plasma calcium concentration sufficiently in order to create room for the use of vitamin D to cure the osteomalacia component of the osteodystrophy and simultaneously block the excessive bone resorption. Therefore, five patients with renal osteodystrophy and hypercalcemia were treated for up to 9 months with APD. Three of them, who were on chronic hemodialysis, received 15 mg APD i.v. 3 times a week, the 2 other patients with severe renal failure received 200 mg APD orally. Ionized calcium in plasma did not decrease. Histological investigation of bone samples, obtained before and after therapy, showed an increase of fibrous tissue and a remarkable increase in the number of osteoclasts or osteoclast-like cells not only along the bone-margin, but mainly within the bone-marrow. We conclude that in patients with renal failure with hypercalcemia, APD in the doses used had no effect on plasma calcium level, but caused a striking change in bone histology. Although the consequences of these findings are not yet clear, they do not seem to indicate improvement of bone structure.

Adult↗

PubMed1990

Value of serum aluminium monitoring in dialysis patients: a multicentre study.

The clinical relevance of regular serum aluminium monitoring in dialysis patients was investigated in a multicentre study by 6-monthly determination of the serum aluminium during 4 consecutive years. In a group totalling 1193 patients, a striking decrease of mean serum aluminium was observed the last 2 years of the study. This phenomenon was accompanied by a substantial reduction of the prescribed dose of aluminium hydroxide (Al(OH)3) and its partial replacement by calcium carbonate (CaCO3) and/or magnesium hydroxide (Mg(OH)2). Under this policy serum phosphate control remained satisfactory. In all the centres, water treatment was found to be adequate, yielding dialysate aluminium around 2 micrograms/l. Dialysis patients with clinically overt liver disease showed a significantly greater median serum aluminium concentration than that observed in a control dialysis population. Compared to the latter group, the median serum aluminium concentration of dialysis patients with diabetes mellitus did not differ significantly. Results further indicated that patients with biopsy-proven osteomalacia presented a significantly greater median serum aluminium compared to that of patients without osteomalacia. We demonstrated that a serum aluminium of 60 micrograms/l provides a relatively sensitive (82%) and specific (86%) index for the detection of aluminium-related bone disease (ARBD). Provided the aluminium determinations are performed by a qualified laboratory, serum monitoring in dialysis patients (a) allows the safer use of aluminium-containing phosphate binders, and (b) is of value in the diagnosis of overload/toxicity.

Adult↗

PubMed1990

Iron overload and bone disease in chronic dialysis patients.

Bone pathology was studied in 27 patients showing either iron or aluminium accumulation in bone. These patients belonged to a group of 120 unselected chronic haemodialysis patients in whom transiliac bone biopsies had been obtained. Group A consisted of 12 patients with bone iron deposits (positive Perls' staining at the calcified bone boundary, CBB) and only minimal aluminium accumulation (bone aluminium below 20 micrograms/g wet weight). Group B included 15 patients with pronounced aluminium accumulation (positive aluminium staining at the CBB and bone aluminium of 20 micrograms/g wet weight or more) and without significant bone iron deposition (negative Perls' staining at the CBB). Bone diseases were classified as early hyperparathyroidism, osteitis fibrosa, mixed disease, osteomalacia, adynamic bone disease or other bone condition using osteoid volume, relative osteoblastic activity (ROBA%), and the presence of fibrosis, as criteria. In group A, 5 of 12 patients showed adynamic bone disease, a fairly uncommon condition in the general population of non-parathyroidectomised dialysis patients. In fact, in a control group of 80 patients without iron and without aluminium overload, only five patients showed adynamic bone disease. In group B, 8 of 15 patients showed osteomalacia, and 2 of 15 presented with mixed disease, which is in agreement with the established relationship between bone aluminium accumulation and the occurrence of defective bone mineralisation. It is concluded that iron overload in dialysis patients is associated with an increased frequency of adynamic bone disease.

Aluminum↗

PubMed1990

Osteoporosis and diabetes: lessons from the diabetic BB rat.

The spontaneously diabetic BB rat was used to study the effect of diabetes on bone. Short-term diabetes (3-4 weeks) resulted in a state of low bone turnover, characterized by a severe decrease in osteoblast/osteoid surface and bone mineral apposition rate on histology, and in serum osteocalcin concentrations. If diabetes was long-term (12 weeks), the parameters of low bone formation were associated with histological evidence of osteoporosis and a decreased bone strength; the relative bone calcium concentration remained normal in diabetes. We conclude that long-standing diabetes results in a low-turnover osteoporosis.

Animals↗

PubMed1990

Bone and mineral metabolism in BB rats with long-term diabetes. Decreased bone turnover and osteoporosis.

The effect of long-term diabetes mellitus on bone and mineral metabolism was studied in BB rats. Diabetic rats were treated with 1 U of long-acting insulin every other day for 12 wk and compared with nondiabetic littermates. Urinary calcium excretion was increased greater than 10-fold, but serum total and diffusible calcium remained normal. Serum concentrations of both 1 alpha, 25-dihydroxyvitamin D3 and vitamin D-binding protein were significantly decreased in diabetic rats. The intestinal calbindin-D 9K concentration was decreased by nearly 50%, and active duodenal calcium absorption was totally abolished. Trabecular bone volume measured in the tibial metaphysis was decreased by 44%, and the osteoblast and osteoid surfaces were less than 10% of values observed in control rats, whereas the osteoclast surface was unchanged by diabetes. The daily bone formation (bone mineral apposition rate) measured by labeling twice with calcein was decreased by 86% in diabetic rats. The serum concentration of osteocalcin, a biochemical marker of osteoblast function, was similarly decreased (mean +/- SE 23 +/- 3 and 62 +/- 4 micrograms/L in diabetic [n = 15] and nondiabetic [n = 15] rats, respectively). Serum osteocalcin was significantly correlated with the serum concentration of insulinlike growth factor I (r = 0.89, P less than 0.001). Bone strength measured as the energy needed to fracture the femur was markedly decreased (5.3 +/- 1.4 and 8.4 +/- 1.3 N.m.degree in diabetic and nondiabetic rats, respectively; P less than 0.01). These histological, chemical, and biomechanical data clearly indicate that long-standing diabetes in BB rats results in severe low-turnover osteoporosis probably related to decreased osteoblast recruitment and/or function.

Animals↗

PubMed1989

Peroxidative stress and in vitro ageing of endothelial cells increases the monocyte-endothelial cell adherence in a human in vitro system.

Adherence of monocytes to the endothelium is an early event in atherogenesis. Changes in the endothelium are probably involved in this process. We have investigated the influence of peroxidative stress and in vitro ageing of endothelial cells on the subsequent adherence of monocytes using an in vitro system. Treatment of young human umbilical vein endothelial cells (HUVEC) with 60 microM cumene hydroperoxide (Chp) resulted in a 2.1-fold increase in monocyte adherence. This increase was not dependent on de novo synthesis of membrane antigens. No such increase upon Chp treatment was observed using young human umbilical artery endothelial cells (HUAEC) and in vitro aged HUVEC and HUAEC. As compared with "young" HUVEC, a higher spontaneous adherence of monocytes to "young" HUAEC (1.8 times), "aged" HUVEC (2.5 times) and "aged" HUAEC (2.7 times) was observed. Furthermore, fibroblasts showed an about 3 times higher monocyte adherence, whereas an 8 times higher adherence was observed to endothelial extracellular matrix. These data suggest that the spontaneous monocyte adherence to "young", intact endothelium can be increased by peroxidative damaging and by ageing of the endothelial cells. A denudation and subsequent exposure of the extracellular matrix may further stimulate this process. The possible physiological vector for endothelial peroxidation is discussed.

Arteriosclerosis↗

PubMed1989

Bone mineral homeostasis in spontaneously diabetic BB rats. II. Impaired bone turnover and decreased osteocalcin synthesis.

Bone morphology and function were studied in male spontaneously diabetic BB rats after 3-4 weeks of diabetes. The tibia and lumbar vertebrae weights were decreased, but the bone calcium percentage remained normal. Bone volumes in the tibial metaphysis and the first lumbar vertebra were normal on quantitative histomorphometry. Osteoclast, osteoblast, and osteoid surface percentages, however, and the calculated daily mineral apposition rate in the tibia (1.0 +/- 0.4 vs. 5.6 +/- 0.6 microns/day) and vertebra (0.2 +/- 0.1 vs. 2.3 +/- 0.2 microns/day) were all severely decreased in diabetic rats. Plasma osteocalcin concentrations were also markedly decreased in diabetic rats (24 +/- 2 vs. 108 +/- 10 ng/ml); the half-times of [125I]osteocalcin were similar in diabetic and nondiabetic rats, indicating that decreased plasma osteocalcin was due to decreased synthesis. Plasma osteocalcin levels were more decreased than expected from their suppressed 1,25-dihydroxyvitamin D3 levels, and 1,25-dihydroxyvitamin D3 injections did not increase plasma osteocalcin in diabetic rats as they did in nondiabetic rats. Bone osteocalcin content was normal in diabetic rats. Photon absorptiometry of tibiae showed a similar bone mineral content in diabetic and nondiabetic rats. Biomechanical properties of diabetic rat femora were all in the normal range. Nondiabetic semistarved rats with the same body weight as diabetic rats exhibited a similar delay in bone growth as diabetic rats, but the osteoblast and osteoid surfaces were normal, and the mineral apposition rate was normal (tibia) or slightly decreased (vertebra). Plasma osteocalcin concentrations were also normal in semistarved rats. Thus, the number and/or function of osteoblasts are severely suppressed in diabetes, and this results in decreased osteoid surface, mineral apposition rate, and plasma osteocalcin levels; moreover, these changes cannot be explained by simple weight loss.

Animals↗