Diabetic Osteopenia Research Articles

Osteopenia in insulin-dependent diabetes mellitus; prevalence and aspects of pathophysiology.

The objective was to evaluate the prevalence and severity of osteopenia in patients with uncomplicated insulin-dependent diabetes mellitus (IDDM) and to obtain more information on the pathophysiology of diabetic osteopenia. In 35 patients with uncomplicated IDDM (21 men and 14 women; age 37.6+/-9.9 yr; duration of disease 8.5+/-3.5 years) bone mineral density was measured by dual energy X-ray absorptiometry (DEXA). In addition, markers of bone formation [plasma insulin-like growth factor I (IGF-I), serum alkaline phosphatase (ALP), serum bone alkaline phosphatase (BAP) and serum osteocalcin] and bone resorption [urinary excretion of calcium and of the cross-linked N-telopeptide of type 1 collagen, both corrected for the excretion of creatinine] were measured in the diabetic patients and in 33 healthy controls, matched for sex, age, height, weight and body mass index (BMI). In 67% of the diabetic men and 57% of the diabetic women osteopenia of the femoral neck and/or the lumbar spine (T-value < or = -1 SD) was present. Fourteen percent of the male patients, but none of the female patients, met the criteria for osteoporosis (T-value < or = -2.5 SD). In the whole group of diabetic patients the mean plasma IGF-I level tended to be lower (p<0.10) as compared to that in the controls. In the diabetic patients with femoral neck osteopenia, the mean plasma IGF-I level was significantly lower (p<0.05) than in those without osteopenia at this site. There were no differences in the mean serum ALP, BAP and osteocalcin levels between the diabetic patients and the controls, nor between the diabetic patients with and without femoral neck osteopenia. Considering only the male diabetic patients, significantly lower mean plasma IGF-I (-26%), serum ALP (-24%) and serum osteocalcin (-38%) levels were present in the patients with femoral neck osteopenia than in those without osteopenia at this site, suggesting lowered bone formation. The bone resorption markers were similar in all (sub)groups of diabetic patients and not different between diabetic patients and controls. Bone mineral density (BMD) did not correlate with plasma levels of glycosylated hemoglobin (HbA1c). BMD values were not related to any of the bone resorption or formation markers, except for plasma IGF-I both in the femoral neck (r=+0.38, p=0.026) and the lumbar spine (r=+0.34, p=0.043). Our data demonstrate that at least in male patients with IDDM, osteopenia is the consequence of a lowered bone formation with a predominance of bone resorption over formation.

High insulin and low IGF-I plasma levels following pancreas transplantation in rats. Implications for bone and mineral metabolism

Primary disturbances in mineral metabolism and deficiencies in insulin and insulin-like growth factor-I (IGF-I) have been implicated in the pathogenesis of diabetic osteopenia. This prompted us to investigate whether normal bone minerals and bone morphology are preserved after pancreas transplantation. To this end, 8 inbred rats (transplants) were compared with 9 sham-operated rats (controls) 20 months after orthotopic pancreas transplantation. While basal levels of insulin remained unaffected by transplantation, an oral glucose load elicited hyperinsulinemia (integrated incremental response: mean +/- SEM, 62+/-8 nmol l(-1) 60 min in transplants vs. 32+/-6 nmol l(-1) 60 min in controls; p<0.01) in the presence of normal glucose levels. Fecal and urinary excretion and fractional intestinal absorption of calcium, magnesium and phosphorus, net calcium absorption and the respective serum mineral levels were unchanged after transplantation, as were those of the calciotropic hormones. Serum osteocalcin and bone alkaline phosphatase remained unaffected, and urinary excretion of pyridinium and deoxypyridinium were unchanged. Fasting plasma IGF-I concentration was significantly decreased in transplants (930+/-42 ng ml(-1)) vs. control rats (1074+/-49 ng ml(-1); p < 0.05). Despite similar physical and chemical properties of bone in both groups, histomorphometry revealed slight osteopenia in transplant rats, as reflected by a 38% reduction in the cancellous bone area of the proximal tibial metaphysis. Plasma IGF-I levels were significantly correlated with bone mineral apposition rate (r=0.70, p<0.02), osteoblast perimeter (r=0.60, p<0.05) and osteoid perimeter (r=0.60, p<0.05). In conclusion, pancreas transplantation preserves physical and chemical properties of bone, but bone metabolism is not completely normal after transplantation, as evidenced by decreased cancellous bone. This might have resulted from the insulin resistance associated with the lowering of the plasma IGF-I level, which was correlated with the mineral apposition rate.

Advanced glycation endproduct-specific receptors in rat and mouse osteoblast-like cells: regulation with stages of differentiation.

Advanced glycation endproducts have been implicated in the development of diabetic complications. In addition, these products could also mediate certain bone alterations such as diabetic osteopenia. Several receptors specific for advanced glycation endproduct-modified proteins have been characterized in different cell types, contributing to the recognition and degradation of senescent proteins. In the present report, we investigated the possible presence of advanced glycation endproduct-binding proteins on osteoblast-like cells. Both UMR106 and MC3T3E1 cell lines express specific advanced glycation endproduct-binding sites, with an affinity constant between 0.4 and 1.7. 10(6) M(-1), depending on the stage of osteoblastic differentiation; and with a receptor capacity of 1.5-2.0. 10(7) sites/cell. Osteoblast-like cells were also found to participate both in the uptake and degradation of advanced glycation endproduct-modified bovine serum albumin at 37 degrees C. Radiolabelled ligand blotting studies confirmed the presence of several membrane binding proteins, with apparent molecular masses of 50, 45-40, 30, 25 and 18 kDa; the major bands corresponded to 30 and 25 kDa proteins. This study provides evidence of the presence of advanced glycation endproduct-specific binding sites, and for their regulation with the stage of differentiation, in two osteoblast-like cells in culture.

Protective effect of an aldose reductase inhibitor against bone loss in galactose-fed rats: Possible involvement of the polyol pathway in bone metabolism

Many patients with diabetes mellitus show a moderate reduction in bone mass. Our recent in vitro studies showed that sustained exposure of osteoblast-like MG-63 cells to high glucose by itself impairs their functions partly via the polyol pathway. To investigate the role of hyperglycemia in the etiology of diabetic osteopenia in vivo separately from insulin deficiency, we determined whether epalrestat, an aldose reductase (AR) inhibitor (ARI), lessens the abnormalities in calcium (Ca) metabolism in galactose-fed rats. Weight gain was impaired in the rats, which was not altered by epalrestat. Galactose feeding temporarily enhanced bone resorption as reflected by increased biochemical markers for bone resorption (urinary excretion of pyridinoline [PYR] and deoxypyridinoline [DPYR]) at 1 to 3 months, which were significantly decreased by epalrestat. Epalrestat also restored the positive correlation between a bone-formation marker (serum osteocalcin [OC]) and a bone-resorption marker (urinary DPYR excretion) at 6.5 months. Histomorphometric analysis of bone performed 6.5 months after galactose feeding showed that both the bone volume and osteoblast numbers in the tibia, which were significantly suppressed by galactose feeding, were partly restored to a significant extent by the simultaneous administration of epalrestat. In summary, epalrestat partially protected against the development of osteoblast dysfunction and reduced the temporary increase in biochemical markers for bone resorption induced by galactose feeding, with a resultant increase in bone volume, suggesting that the polyol pathway may be intimately involved in the development of abnormal bone metabolism in galactose-fed rats.

Poor glycemic control impairs the response of biochemical parameters of bone formation and resorption to exogenous 1,25-dihydroxyvitamin D3 in patients with type 2 diabetes.

Osteoblast deficit plays a principal role in the development of diabetic osteopenia. We have previously reported that high glucose conditions impair the function of osteoblast-like MG-63 cells. This study was performed to assess the sensitivity of osteoblasts to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in patients with type 2 diabetes without insulin deficiency or overt diabetic complications. During stimulation with 1,25(OH)2D3 at 2.0 micrograms/day for 6 consecutive days in 9 type 2 diabetic patients, serum levels of bone alkaline phosphatase (BALP), osteocalcin (OC) and the carboxyterminal propeptide of type 1 procollagen, and the urinary excretion of pyridinoline and deoxypyridinoline (DPYR), were monitored. As parameters of glycemic control, the mean level of fasting plasma glucose (mFPG) throughout the 1,25(OH)2D3 stimulation test and the level of HbA1C were used. 1,25(OH)2D3 increased serum 1,25(OH)2D significantly by day 2, which was followed by a significant reduction in the serum level of intact parathyroid hormone. The maximal increment of serum OC adjusted for that of 1,25(OH)2D was negatively correlated with both mFPG and HbA1C levels (p < 0.05). Furthermore, the magnitude of 1,25(OH)2D3-induced bone resorption, as reflected by the maximal increase in urinary DPYR excretion, was negatively correlated with the mFPG level (p < 0.05). Basal BALP tended to be negatively correlated with HbA1C, although not to a significant extent. In conclusion, our findings would indicate that poor glycemic control impairs the responses of osteoblasts and osteoclasts to 1,25(OH)2D3 in normo-insulinemic type 2 diabetic patients.

糖尿病性骨減少症

糖尿病性骨減少症

A 2-year follow-up study on bone mineral density and markers of bone turnover in patients with long-standing insulin-dependent diabetes mellitus.

The aim of study was to evaluate, during 2-year follow-up, bone mineral density in sites with different cortical/cancellous bone ratios (lumbar spine, total body, distal site of radius) and selected markers of bone turnover (total alkaline phoshatase, osteocalcin, pyridinoline and deoxypirydinoline) in patients with long-standing insulin-dependent diabetes mellitus in comparison with healthy controls. Additionally, the influence of age, sex, smoking, duration of diabetes, the degree of metabolic control, or coexisting chronic complications of diabetes (retinopathy, incipient nephropathy, polyneuropathy) on the studied indices of bone metabolism in patients with insulin-dependent diabetes mellitus were evaluated. It was found that patients with long-standing diabetes mellitus had significantly lower bone mineral density than healthy controls (p < 0.003 in lumbar spine and p < 0.001 in total body). The incidence rate of osteopenia and osteoporosis was significantly higher in this group of patients in comparison with the controls (p < 0.005 for lumbar spine and total body and p < 0.001 for radius). In comparison with healthy subjects, diabetic patients and significantly higher, but within normal reference range, serum alkaline phosphate (p < 0.005) and osteocalcin (p < 0.05), accompanied by similar pyridinoline and not significantly increased deoxypyridinoline. Duration and metabolic control of diabetes, or the coexistence of its chronic complications, did not correlate with bone mineral density or the studied indices of bone turnover. In conclusion, diabetic osteopenia seems to be a normal bone turnover state, not influenced by the duration or degree of metabolic control of diabetes.

Prospective Bone Mineral Density Evaluation in Patients With Insulin-Dependent Diabetes Mellitus

The bone mineral density (BMD) in patients with insulin-dependent diabetes mellitus (IDDM) was evaluated prospectively to assess the course of osteopenia in IDDM. We measured BMD in the lumbar spine, femoral region, and total body calcium in 23 patients aged 21–53 years with IDDM for 2.3 to 20 years using a dual energy X-ray absorptiometry. A second BMD measurement was done after 26.5 ± 4.1 months in all patients. The blood glucose control, insulin dosage, and disease duration were also assessed. Eleven patients had osteopenia (1 Z-score below the mean values of normal gender- and age-matched individuals). These patients had a longer IDDM duration (8.6 ± 5.1 years in osteopenics versus 4.6 ± 3.75 years in non-osteopenics; p = 0.03). The blood glucose control and insulin dosage were not significantly different throughout the study. The mean spinal BMD was higher in the second evaluation in both osteopenics (0.91 ± 0.12 g/cm 2 and 0.96 ± 0.09 g/cm 2, p = 0.035) and non-osteopenics (1.24 ± 0.15 g/cm 2 and 1.29 ± 0.16 g/cm 2; p = 0.02). In the end of the study, however, the osteopenic group persisted with lower subnormal BMD values than the non-osteopenic group ( p < 0.001). The small BMD increment observed in the spine did not correlate with changes in the metabolic control or with IDDM duration, but occurred mainly in patients younger than 30 years old. There was no significant change in the femoral BMD or total body calcium. None of the patients developed or significantly worsened the osteopenia. We conclude that diabetic osteopenia, despite being a complication of high prevalence in IDDM, seems to be non-progressive in the majority of patients. In some patients, the spinal BMD increased during observation and may have been due to achievement of peak bone mass.

Growth-Inhibitory Effect of a High Glucose Concentration on Osteoblast-like Cells

Impaired bone formation resulting from a decline of osteoblast activity has been implicated in the pathogenesis of diabetic osteopenia. We examined the effects of high glucose concentration alone, independent of insulin deficiency, on the growth of a human osteoblast-like cell line (MG-63). Sustained exposure to high glucose for 7 days inhibited cell growth in a concentration-dependent manner up to 49.5 mmol/L, as compared with cells cultured with a normal glucose concentration (5.5 mmol/L) or a high mannitol concentration (an iso-osmolar control). Glucose (49.5 mmol/L) attenuated the increment either in DNA content or in [ 3H]thymidine incorporation induced by insulin-like growth factor I (IGF-I). The IGF-I-induced increase of ornithine decarboxylase (ODC) activity, which plays an important role in cell growth, was also attenuated. The half-life of ODC protein was not shortened by the high glucose culture, but the intracellular content of putrescine (an end product of ODC) was significantly decreased. These changes did not occur in the high mannitol culture, strongly suggesting a specific effect of glucose. In summary, our observations suggest that a high glucose concentration significantly impairs the proliferative response of osteoblastic cells to IGF-I and that the defective cell function caused by sustained exposure to high glucose levels might contribute to impaired bone formation in patients with diabetic osteopenia.

Bone Mineral Density and Bone Metabolism in Diabetes Mellitus

The effect of diabetes mellitus on bone metabolism and bone mineral density is discussed controversially. Diabetes mellitus due to an autoimmune process seems to be associated with low turnover osteopenia either in the animal model or in children and adolescents. A number of factors are discussed as being involved, but in this age group clinical symptoms are missing. Adult patients of either sex with IDDM show a reduced bone mineral density when measured at peripheral sites such as the distal forearm or the femoral neck, diabetic complications such as neuropathy and microangiopathy seem to pronounce the deficit of bone mass. In these patients, osteopenia is accompanied by a high turnover situation of bone metabolism, possibly due to microvascular complications. In contrast, patients with NIDDM and here especially overweight women have a normal or even increased bone mineral density. Up to now, there is no convincing evidence for an increased incidence of osteoporotic fractures in diabetic patients. Systemic diabetic osteopenia therefore does not seem to be of great epidemiological relevance.

Importance of sustained high glucose condition in the development of diabetic osteopenia: possible involvement of the polyol pathway.

Importance of sustained high glucose condition in the development of diabetic osteopenia: possible involvement of the polyol pathway.

Role of nonenzymatic glycosylation of type I collagen in diabetic osteopenia.

Formation of advanced glycation end products (AGEs) in extracellular matrix (ECM) is implicated in the development of chronic diabetic complications. However, the involvement of AGEs in diabetic bone disease has not been well established. We have examined whether AGEs are increased in the bone collagen of streptozotocin-induced diabetic rats in vivo and whether glycation of type I collagen affects the functions of osteoblastic cells in vitro. During 12 weeks of observation, AGEs in collagen extracted from the tibiae of diabetic rats increased in a time-dependent manner and were significantly higher than controls at every time point. In vitro, the incubation of collagen with glucose-6-phosphate resulted in a time-dependent increase of AGEs. When osteoblastic cells isolated from fetal rat calvaria were cultured on AGE-modified type I collagen, it dose-dependently inhibited phenotypic expressions of osteoblasts. Among osteoblastic parameters, nodule formation was the most sensitive, being inhibited by approximately 70% by the glycation of collagen for only 1 week. Alkaline phosphatase activity and osteocalcin secretion were inhibited by 20-30% and 15-70%, respectively, by the glycation of collagen for 1-5 weeks. These results indicate that AGE-modified collagen affects osteoblastic cell differentiation and function in vitro and suggest that similar changes occurring in vivo may contribute to diabetic osteopenia.

Bone mineral density measured by dual X-ray absorptiometry in Spanish patients with insulin-dependent diabetes mellitus.

Previous studies suggest that low bone mass is a potential complication of insulin-dependent diabetes mellitus. Nevertheless, the factors that influence diabetic osteopenia are not well established. In order to evaluate the prevalence and magnitude of diabetic osteopenia and its association with clinical and metabolic variables, we studied 94 consecutive patients with insulin-dependent diabetes mellitus. Their age ranged from 20 to 56 years and duration of diabetes varied from 1 to 35 years. Bone mineral density (BMD) was measured by dual X-ray absorptiometry at lumbar spine and proximal femur and the values were expressed as z-score. The presence and extent of microvascular complications, degree of metabolic control, and other risk factors for osteoporosis were recorded and some biochemical markers of bone metabolism were assessed. Diabetic patients showed reduced BMD in all sites (lumbar spine: -0.89 +/- 1.21; femoral neck: -0.99 +/- 1.24; Ward triangle: -1.05 +/- 1.24; P < 0.0001). Of the 94 patients 19.1% met diagnostic criteria for osteoporosis. BMD correlated with body mass index in all sites and with the duration of disease in Ward's triangle. Presence and extent of diabetic complications were associated with lower BMD, as was smoking. No correlation was found between BMD and biochemical markers. In conclusion, osteopenia is a common complication in patients with insulin-dependent diabetes mellitus. Microvascular complications are a critical point in the progression of diabetic osteopenia. Other risk factors for osteoporosis (nutritional status and smoking) must be taken into account.

Increasing serum osteocalcin after glycemic control in diabetic men.

The pathogenesis of diabetic osteopenia is unclear. The markers of bone metabolism may show some changes in diabetic patients. In this study, we investigated the effect of glycemic control on serum osteocalcin level and urinary hydroxyproline excretion and the relations of these markers to duration of diabetes, C-peptide status, and body mass index. Twenty-seven men with poorly controlled diabetes mellitus (DM) (HbA1 > 9%, fasting plasma glucose > 7.8 mmol/liter) between ages 25 and 60 years (means +/- SD 46.6 +/- 10.4) were included in the study. Duration of diabetes was 5.8 +/- 4.7 years, body mass index (BMI) was 25 +/- 3.5 kg/m2, and fasting C-peptide was 2.33 (1.05-3.21) micrograms/liter. None of the patients had a disease or were treated with drugs that would interfere with calcium or phosphate metabolism and/or bone structure. They were free from chronic diabetic complications. Of these patients, 11 were lost to follow-up before metabolic control was achieved. The remaining 16 patients obtained good glycemic control (HbA1 < 8.3%, fasting plasma glucose < 7.8 mmol/liter) and completed the study. Serum osteocalcin level and urinary hydroxyproline excretion were determined before and after glycemic control. Urinary hydroxyproline excretion was not significantly changed by glycemic control [17.8 (7.1-23.2) versus 18.1 (10.9-28.1) mg/m2 day, P > 0.05]. However, serum osteocalcin level was significantly elevated (5.04 +/- 1.43 versus 4.17 +/- 1.83 micrograms/liter, P = 0.04). We found no correlation among fasting plasma glucose, HbA1, and fasting serum C-peptide levels with urinary hydroxyproline excretion. There was also no correlation between serum osteocalcin and fasting plasma glucose or serum C-peptide, but HbA1 was negatively correlated with serum osteocalcin (P = 0.01). No correlation was found between DM duration and BMI in the patients with serum osteocalcin level and urinary hydroxyproline excretion. To eliminate the possible effect of exogenous insulin on bone metabolism, the correlation analysis between the markers and C-peptide was further repeated in oral agents-treated patients. Serum C-peptide was not correlated to serum osteocalcin or urinary hydroxyproline in this subgroup of patients. Knowing that serum osteocalcin is a marker of bone formation, we concluded that osteoblast function may improve by glycemic control in diabetic patients; this may be due to correction of metabolic abnormalities associated with insulinopenia.

Effect of eicosapentaenoic acid and docosahexaenoic acid on diabetic osteopenia

To evaluate the effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are polyunsaturated fatty acids, on diabetic osteopenia, we measured the bone fragility in streptozotocin-induced diabetic rats. The fragility of femur was increased in diabetic rats, which was prevented in part by EPA or DHA. Moreover, EPA prevented osteopenia even in diabetic rats fed a low zinc feed, which was a potent accelerator of diabetic osteopenia. Plasma alkaline phosphatase activity and parathyroid hormone level showed no difference between the two groups of diabetic rats with or without EPA. Urinary excretion of calcium and phosphate was increased and plasma inorganic phosphate level was high in diabetic rats, suggesting severe mineral loss. In diabetic rats fed EPA, although urinary and plasma calcium levels did not change significantly, urinary phosphate excretion and plasma inorganic phosphate concentration were slightly lowered, which suggested that EPA may have an effect in suppressing phosphate release from bones in diabetic rats. These data suggest that EPA and DHA could be effective on diabetic osteopenia, but to elucidate the precise mechanisms, further examinations will be needed.

Sodium clodronate for the treatment of Paget's disease following previous disodium pamidronate

Many patients with diabetes mellitus show a moderate reduction in bone mass. Our recent in vitro studies showed that sustained exposure of osteoblast-like MG-63 cells to high glucose by itself impairs their functions partly via the polyol pathway. To investigate the role of hyperglycemia in the etiology of diabetic osteopenia in vivo separately from insulin deficiency, we determined whether epalrestat, an aldose reductase (AR) inhibitor (ARI), lessens the abnormalities in calcium (Ca) metabolism in galactose-fed rats. Weight gain was impaired in the rats, which was not altered by epalrestat. Galactose feeding temporarily enhanced bone resorption as reflected by increased biochemical markers for bone resorption (urinary excretion of pyridinoline [PYR] and deoxypyridinoline [DPYR]) at 1 to 3 months, which were significantly decreased by epalrestat. Epalrestat also restored the positive correlation between a bone-formation marker (serum osteocalcin [OC]) and a bone-resorption marker (urinary DPYR excretion) at 6.5 months. Histomorphometric analysis of bone performed 6.5 months after galactose feeding showed that both the bone volume and osteoblast numbers in the tibia, which were significantly suppressed by galactose feeding, were partly restored to a significant extent by the simultaneous administration of epalrestat. In summary, epalrestat partially protected against the development of osteoblast dysfunction and reduced the temporary increase in biochemical markers for bone resorption induced by galactose feeding, with a resultant increase in bone volume, suggesting that the polyol pathway may be intimately involved in the development of abnormal bone metabolism in galactose-fed rats.

Diabetic osteopenia: pathophysiology and clinical aspects.

Diabetes/Metabolism ReviewsVolume 11, Issue 1 p. 21-35 Article Diabetic osteopenia: Pathophysiology and clinical aspects Yutaka Seino, Corresponding Author Yutaka Seino Department of Metabolism and Clinical Nutrition, Kyoto University School of Medicine, Kyoto, JapanDepartment of Metabolism and Clinical Nutrition, Kyoto University School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-Ku, Kyoto 606, Japan.Search for more papers by this authorHitoshi Ishida, Hitoshi Ishida Department of Metabolism and Clinical Nutrition, Kyoto University School of Medicine, Kyoto, JapanSearch for more papers by this author Yutaka Seino, Corresponding Author Yutaka Seino Department of Metabolism and Clinical Nutrition, Kyoto University School of Medicine, Kyoto, JapanDepartment of Metabolism and Clinical Nutrition, Kyoto University School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-Ku, Kyoto 606, Japan.Search for more papers by this authorHitoshi Ishida, Hitoshi Ishida Department of Metabolism and Clinical Nutrition, Kyoto University School of Medicine, Kyoto, JapanSearch for more papers by this author First published: April 1995 https://doi.org/10.1002/dmr.5610110103Citations: 49AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume11, Issue1April 1995Pages 21-35 RelatedInformation

Amylin increases bone volume but cannot ameliorate diabetic osteopenia.

Amylin is normally secreted in a regulated fashion by the pancreatic beta-cells in parallel with insulin and has been reported to have bone-conserving properties. Type I diabetes mellitus results in a low-turnover osteopenia in the presence of decreased amylin, which is in contrast to type II diabetes where less bone loss, in the presence of high amylin levels, occurs. We investigated the effects of amylin on bone mineral metabolism in normal and diabetic (streptozotocin-induced) rats, in order to ascertain whether amylin would modify the streptozotocin-induced diabetic osteopenia. Ten-week-old male Sprague-Dawley rats were randomized as follows: group A (n = 18) received normal saline; group B (n = 18) received amylin; group C, diabetic rats (n = 23), received normal saline; and group D, diabetic rats (n = 23), received amylin. Amylin (100 pmol/100 g b.w.) was administered by a daily subcutaneous injection. Double calcein-labeled tibiae were removed for histomorphometric analysis followed sacrifice on day 19. Results showed no difference in blood ionized calcium between groups. Blood glucose remained above 600 mg/dl in the diabetic animals and was not affected by the administration of amylin. Serum osteocalcin, insulin-like growth factor-1 (IGF-1), parathyroid hormone (PTH), and 1,25 dihydroxyvitamin D [1,25(OH)2D] were significantly lower in the diabetic rats compared with control group A by day 19. Amylin produced higher levels of serum osteocalcin in group B on day 9 (P < 0.05) compared with controls but returned to control values (group A) by day 19; no such change occurred in the diabetic group.(ABSTRACT TRUNCATED AT 250 WORDS)

A study of osteopenia in elderly diabetic patients

It is well known that IDDM cases can be complicated with osteopenia, but most of these results were reported using single photon absorptiometry. There have been few reports of diabetic osteopenia using dual energy X-ray absorptiometry (DXA), a method that is excellent for precise bone mineral measurement. Osteoarthritis and osteophytes of unknown origin in the lumbar vertebrae are often observed in elderly NIDDM patients. In this study, we examined the clinical characteristics of decreased bone mineral density (BMD) and whether anteroposterior (AP) scanning of the lumbar vertebrae (L2-L4) provides sufficient informations concerning osteopenia in elderly diabetic patients. The study was performed using DXA, which can quantify regional BMD throughout the body. The BMD in the total body and that in the lumbar vertebrae were measured by DXA (Lunar Co.) in 68 diabetics over age 60, 33 males and 35 females, mean age 68 +/- 8 yr, (mean +/- SD) and in 94 middle-aged diabetics (40 to 59), 56 males and 38 females, mean age 51 +/- 4 yr. The percentage of decrease in regional BMD in diabetic patients differed significantly by age and gender. The BMD in the head and spine especially decreased after menopause in women. However, the BMD of the leg and spine did not decrease with age in men. When the BMD of the lumbar vertebrae was plotted against the Y axis and the BMD in the total body against the X axis, the slope of the curve showed a greater increase in elderly diabetics than that in middle aged diabetics (1.8 vs 1.5) suggesting the BMD in the lumbar vertebrae has been overestimated.(ABSTRACT TRUNCATED AT 250 WORDS)

Hip and distal arm fracture rates in peri- and postmenopausal insulin-treated diabetic females.

Hip and distal arm fractures are associated with osteoporosis in the postmenopausal female. In diabetic patients, bone mass has been found to be reduced leading to the hypothesis that diabetes is a risk factor for osteoporosis. Whether this has any clinical implication has only been sparsely elucidated. A cross-sectional case-control study. All insulin-treated diabetic females above the age of 40 years who regularly visited the Steno Memorial Hospital out-patient clinic in 1989. Peri-and postmenopausal females from the general population living in a similar suburban region of Copenhagen admitted to Glostrup University Hospital because of a hip or Colles' fracture between 1 January 1989 and 31 October 1990. The study comprised 748 insulin-treated diabetic females. Thirty hip fractures and 82 Colles' fractures were reported after the age of 40 years. Out of 26,564 females from the general population, 622 were admitted to Glostrup hospital because of a hip or Colles' fracture. METHODS/INTERVENTION: Answers based on questionnaires sent to all diabetic females, and the use of hospital files and hospital registers. In diabetic females aged 40-49 years, Colles' fracture rate was 2/1000 years and hip fracture rate 0.43/1000 years. Fracture rate increased with age and, amongst 80-89-year-old diabetic females, the frequency of both fracture rates was 31/1000 years. These rates were slightly lower than the rates in the general female population. The relative risk of Colles' fracture in diabetic females aged 40-49 years was 0.3 +/- 0.2 (95% confidence limits) and that of hip fracture 1.0 +/- 1.1. In diabetic females aged 80-89 years, the risk of Colles' fracture and hip fracture were 1.3 +/- 1.1 and 1.0 +/- 0.9. Fracture rate was not associated with the development of diabetic complications, long-term metabolic control, or age at diagnosis. Our results suggest that diabetic osteopenia does not have any clinical impact on fracture risk.