Metaphyseal Bone Mineral Density Research Articles

Forearm bone mineral density as a predictor of reduction loss in distal radius fractures treated with cast immobilization.

Many potential predictors have been identified and proposed for predicting late reduction loss in distal radius fractures. However, no report exists on whether the bone mineral density (BMD) of the forearm correlates with the loss of reduction in distal radius fractures. This study aimed to investigate whether forearm BMD can be used as a predictor of reduction loss in distal radius fractures treated with cast immobilization. Ninety patients with distal radius fractures were divided into two groups according to the maintenance or loss of reduction evaluated from radiographs taken at least 6 weeks after their injury. Lumbar and forearm BMD (total and metaphysis) T-scores were measured and compared between the maintenance of reduction (MOR) group and the loss of reduction (LOR) group. Additionally, serologic markers (C-terminal telopeptide, osteocalcin, vitamin D) and radiologic risk factors (intra-articular fracture, ulnar fracture, dorsal comminuted fracture, volar hook) were evaluated and a logistic multiple regression analysis was performed to know the main risk factors of reduction loss. Reduction loss was observed in 38 patients (42.2%). The total and metaphyseal BMD of the forearm was less in the LOR group than in the MOR group. However, the difference was not statistically significant [-2.9 vs. -2.5 for total (p = 0.18), -2.3 vs. -2.0 for metaphysis (p = 0.17)]. Multiple logistic regression analysis showed initial dorsal comminution (p = 0.008) and ulnar variance (p = 0.01) were the main risk factors for reduction loss. Forearm BMD was not a valuable prognostic factor for reduction loss in distal radius fractures. Initial dorsal comminution and ulnar variance rather than forearm BMD should be considered preferentially when predicting which patients are at high risk of reduction loss in distal radius fractures.

Long Bone Mineral Loss, Bone Microstructural Changes and Oxidative Stress After Eimeria Challenge in Broilers.

The objective of this study was to evaluate the impact of coccidiosis on bone quality and antioxidant status in the liver and bone marrow of broiler chickens. A total of 360 13-day old male broilers (Cobb 500) were randomly assigned to different groups (negative control, low, medium-low, medium-high, and highest dose groups) and orally gavaged with different concentrations of Eimeria oocysts solution. Broiler tibia and tibia bone marrow were collected at 6 days post-infection (6 dpi) for bone 3-D structural analyses and the gene expression related to osteogenesis, oxidative stress, and adipogenesis using micro-computed tomography (micro-CT) and real-time qPCR analysis, respectively. Metaphyseal bone mineral density and content were reduced in response to the increase of Eimeria challenge dose, and poor trabecular bone traits were observed in the high inoculation group. However, there were no significant structural changes in metaphyseal cortical bone. Medium-high Eimeria challenge dose significantly increased level of peroxisome proliferator-activated receptor gamma (PPARG, p < 0.05) and decreased levels of bone gamma-carboxyglutamate protein coding gene (BGLAP, p < 0.05) and fatty acid synthase coding gene (FASN, p < 0.05) in bone marrow. An increased mRNA level of superoxide dismutase type 1 (SOD1, p < 0.05) and heme oxygenase 1 (HMOX1, p < 0.05), and increased enzyme activity of superoxide dismutase (SOD, p < 0.05) were found in bone marrow of Eimeria challenged groups compared with that of non-infected control. Similarly, enzyme activity of SOD and the mRNA level of SOD1, HMOX1 and aflatoxin aldehyde reductase (AKE7A2) were increased in the liver of infected broilers (p < 0.05), whereas glutathione (GSH) content was lower in the medium-high challenge group (p < 0.05) compared with non-challenged control. Moreover, the mRNA expression of catalase (CAT) and nuclear factor kappa B1 (NFKB1) showed dose-depend response in the liver, where expression of CAT and NFKB1 was upregulated in the low challenge group but decreased with the higher Eimeria challenge dosage (p < 0.05). In conclusion, high challenge dose of Eimeria infection negatively affected the long bone development. The structural changes of tibia and decreased mineral content were mainly located at the trabecular bone of metaphyseal area. The change of redox and impaired antioxidant status following the Eimeria infection were observed in the liver and bone marrow of broilers.

Proximal femoral changes related to obesity: an analysis of slipped capital femoral epiphysis pathoanatomy.

Recent research has revealed the importance of the femoral epiphyseal tubercle and cupping height in the stability of the physis and its association with capital femoral slippage. To better understand the connection between the pathogenesis of slipped capital femoral epiphysis and obesity, we performed a retrospective analysis of proximal femur and acetabular anatomies using computed tomography (CT) scans in the hips of normal weight and obese pediatric patients. We measured morphologic characteristics of the proximal femur and acetabulum in developing hips of 31 obese adolescent patients and age-matched and sex-matched control group using pelvic CT scans. Measurements included physeal diameter, tubercle height, width, and volume, cupping height, acetabular rotation and inclination, and metaphyseal bone density. Measurements were performed on true coronal and sagittal views through the center of the epiphysis using previously described and validated techniques. Statistical analysis was performed to compare the measurements between obese and nonobese adolescents. The epiphyseal tubercle volume and average cupping size were similar between the two groups. Acetabular inclination and metaphyseal bone density were significantly different between the cohorts. Metaphyseal bone density was lower among obese patients. Obesity does not appear to cause morphologic changes to the capital femoral physis, though it is associated with a decreased metaphyseal bone mineral density which could indicate physeal instability. This could suggest increased metabolic activity in the metaphyseal bone in obese adolescents. Therefore, metabolic factors associated with obesity, rather than anatomical changes, may be responsible for physeal instability seen in obese adolescents.

Proximal tibial trabecular bone mineral density is related to pain in patients with osteoarthritis

BackgroundOur objective was to examine the relationships between proximal tibial trabecular (epiphyseal and metaphyseal) bone mineral density (BMD) and osteoarthritis (OA)-related pain in patients with severe knee OA.MethodsThe knee was scanned preoperatively using quantitative computed tomography (QCT) in 42 patients undergoing knee arthroplasty. OA severity was classified using radiographic Kellgren-Lawrence scoring and pain was measured using the pain subsection of the Western Ontario and McMaster Universities Arthritis Index (WOMAC). We used three-dimensional image processing techniques to assess tibial epiphyseal trabecular BMD between the epiphyseal line and 7.5 mm from the subchondral surface and tibial metaphyseal trabecular BMD 10 mm distal from the epiphyseal line. Regional analysis included the total epiphyseal and metaphyseal region, and the medial and lateral epiphyseal compartments. The association between total WOMAC pain scores and BMD measurements was assessed using hierarchical multiple regression with age, sex, and body mass index (BMI) as covariates. Statistical significance was set at p < 0.05.ResultsTotal WOMAC pain was associated with total epiphyseal BMD adjusted for age, sex, and BMI (p = 0.013) and total metaphyseal BMD (p = 0.017). Regionally, total WOMAC pain was associated with medial epiphyseal BMD adjusted for age, sex, and BMI (p = 0.006).ConclusionThese findings suggest that low proximal tibial trabecular BMD may have a role in OA-related pain pathogenesis.

Periprosthetic tibial bone mineral density changes after total knee arthroplasty

Background and purpose — Total knee arthroplasty (TKA) may cause postoperative periprosthetic bone loss due to stress shielding. Bone also adapts to mechanical alterations such as correction of malalignment. We investigated medium-term changes in bone mineral density (BMD) in tibial periprosthetic bone after TKA.Patients and methods — 86 TKA patients were prospectively measured with dual-energy X-ray absorptiometry (DXA), the baseline measurement being within 1 week after TKA and the follow-up measurements being at 3 and 6 months, and at 1, 2, 4, and 7 years postoperatively. Long standing radiographs were taken and clinical evaluation was done with the American Knee Society (AKS) score.Results — The baseline BMD of the medial tibial metaphyseal region of interest (ROI) was higher in the varus aligned knees (25%; p < 0.001). Medial metaphyseal BMD decreased in subjects with preoperatively varus aligned knees (13%, p < 0.001) and in those with preoperatively valgus aligned knees (12%, p = 0.02) between the baseline and 7-year measurements. No statistically significant changes in BMD were detected in lateral metaphyseal ROIs. No implant failures or revision surgery due to tibial problems occurred.Interpretation — Tibial metaphyseal periprosthetic bone is remodeled after TKA due to mechanical axis correction, resulting in more balanced bone stock below the tibial tray. The diaphyseal BMD remains unchanged after the initial drop, within 3–6 months. This remodeling process was related to good component survival, as there were no implant failures or revision operations due to tibial problems in this medium-term follow-up.

Effect of one-year post-operative alendronate treatment on periprosthetic bone after total knee arthroplasty. A seven-year randomised controlled trial of 26 patients.

Total knee arthroplasty (TKA) is known to lead to a reduction in periprosthetic bone mineral density (BMD). In theory, this may lead to migration, instability and aseptic loosening of the prosthetic components. Bisphosphonates inhibit bone resorption and may reduce this loss in BMD. We hypothesised that treatment with bisphosphonates and calcium would lead to improved BMD and clinical outcomes compared with treatment with calcium supplementation alone following TKA. A total of 26 patients, (nine male and 17 female, mean age 67 years) were prospectively randomised into two study groups: alendronate and calcium (bisphosphonate group, n = 14) or calcium only (control group, n = 12). Dual energy X-ray absorptiometry (DEXA) measurements were performed post-operatively, and at three months, six months, one, two, four, and seven years post-operatively. Mean femoral metaphyseal BMD was significantly higher in the bisphosphonate group compared with controls, up to four years following surgery in some areas of the femur (p = 0.045). BMD was observed to increase in the lateral tibial metaphysis in the bisphosphonate group until seven years (p = 0.002), and was significantly higher than that observed in the control group throughout (p = 0.024). There were no significant differences between the groups in the central femoral metaphyseal, tibial medial metaphyseal or diaphyseal regions of interest (ROI) of either the femur or tibia. Bisphosphonate treatment after TKA may be of benefit for patients with poor bone quality. However, further studies with a larger number of patients are necessary to assess whether this is clinically beneficial.

Comparable Effects of Alendronate and Strontium Ranelate on Femur in Ovariectomized Rats

This study compared the effects of alendronate (ALN) and strontium ranelate (SR) on bone mineral density (BMD), bone histomorphometry, and biomechanics in ovariectomized (OVX) rats. We randomly assigned 48 3-month-old female Sprague-Dawley rats to four groups: sham, OVX, ALN, and SR. Rats in the OVX, ALN, and SR groups received bilateral OVX. Rats in the ALN and SR groups were orally administrated ALN (7 mg/kg/week) and SR (500 mg/kg/day). Rats in the sham and OVX groups were treated with saline. All treatments continued for 12 weeks. Femoral BMD examination, distal femoral bone histomorphometry analysis, and biomechanical tests at the femoral diaphysis and metaphysis were performed to evaluate the effects of treatments in OVX rats. Results showed that both ALN and SR significantly increased femoral BMD (total femur, diaphyseal BMD, and distal metaphyseal BMD), distal femoral bone histomorphometric parameters (BV/TV, Tb.N, and Tb.Th), and femoral biomechanical parameters (maximum load, failure load, stiffness) compared with the OVX group (P < 0.05). No differences were found between ALN and SR in increasing femoral BMD, distal femoral bone histomorphometric parameters (BV/TV, Tb.N, and Tb.Th), and femoral diaphysis biomechanical parameters (maximum load, failure load, stiffness) (P > 0.05). The SR group was inferior to the ALN group in femoral metaphysis biomechanical parameters (P < 0.05). In conclusion, ALN (7 mg/kg/week) and SR (500 mg/kg/day) have similar effects by increasing BMD, distal femoral bone histomorphometric parameters, and femoral metaphysis biomechanical properties. Although ALN has greater effects than SR on distal femoral metaphysis biomechanical properties, in general, ALN and SR have comparable effects on the femur in OVX rats.

Femoral bone mineral density and bone mineral content in bromocriptine-treated pregnant and lactating rats

Since hyperprolactinemia was found to induce osteopenia in the metaphysis of long bone in non-mated female rats, pregnant and lactating rats with sustainedly high plasma prolactin (PRL) levels might also exhibit some changes in their long bones. We performed a longitudinal study in pregnant, lactating and post-weaning rats, using dual-energy X-ray absorptiometry to demonstrate site-specific changes (i.e., metaphysis vs. diaphysis) in femoral bone mineral density (BMD) and content (BMC). The results showed that femoral metaphyseal BMD and BMC were higher when compared to their age-matched controls during pregnancy, before decreasing in late lactation and post-weaning. On the other hand, femoral diaphyseal BMC increased during pregnancy, early lactating and mid-lactating periods without change during late lactation and post-weaning. After 7 days of bromocriptine administration which inhibited endogenous PRL secretion, the lactation-induced increases in BMC during early and mid-lactating periods were abolished. Moreover, a decrease in metaphyseal BMD during late lactation was restored to the control levels by bromocriptine. However, bromocriptine did not antagonize the pregnancy-induced increases in BMD and BMC. It could be concluded that the effect of PRL on bone was variable during the reproductive periods. While having no effect on femoral BMD and BMC during pregnancy, PRL was responsible for bone gain in early and mid-lactating periods, but induced bone loss during late lactating period.

The Peroxisome Proliferator Activator Receptor Alpha/Delta Agonists Linoleic Acid and Bezafibrate Upregulate Osteoblast Differentiation and Induce Periosteal Bone Formation In Vivo

We showed previously that some actions of prostaglandin E(2) (PGE(2)) on bone are caused by its degradation product, PGA(2), which mediates its effects via a class of nuclear receptors known as the peroxisome proliferator activator receptors (PPARs), suggesting that the PPARs may be involved in the regulation of bone formation. The aims of this study were to determine the effects of PPARalpha/delta agonists on bone in vitro and in vivo. PPAR agonists were examined in vitro using the fibroblastic colony-forming unit (CFU-f) assay. The PPARalpha/delta agonists linoleic acid (LA) and bezafibrate (Bez) were then administered to intact male rats by daily s.c. injection for 12 weeks with either vehicle (10% dimethyl sulfoxide), LA (0.3 mg/kg), or Bez (1 mg/kg). CFU-f assays were performed on stromal cells ex vivo. Bone mineral density (BMD) and serum markers of formation and resorption were measured. Bone histomorphometry was performed at cancellous and cortical bone sites. PPARalpha/delta agonists increased significantly the number of osteoblastic colonies as demonstrated by increased alkaline phosphatase activity, collagen production, and calcification. This increase was typically equal to or greater than that achieved with the known bone anabolic agent PGE(2). In intact male rats, LA and Bez increased metaphyseal BMD by 7% and 11%, respectively. Increased BMD was associated with an increase in total bone area, although no changes were observed in bone formation rate within the trabecular compartment. Serum osteocalcin and osteoprogenitor numbers were increased, whereas there was no change in either tartrate-resistant acid phosphatase 5b or osteoclast number. Both LA and Bez increased cortical bone area by approximately 38%, periosteal perimeter by 15%, and periosteal bone formation by 221% and 140%, respectively. There was no effect on medullary cavity area or endocortical perimeter. These data suggest that PPARalpha/delta may have roles in bone anabolism, specifically in the regulation of periosteal bone formation. They are potential therapeutic targets for osteoporosis therapy.

Influence of Lifelong Soy Isoflavones Consumption on Bone Mass in the Rat

Soy isoflavones (IFs) have shown a bone-sparing effect through epidemiological studies in the Asian population. However, there is no evidence as to whether such protection would result from a lifelong exposure. We investigated the impact of an early exposure to IFs on bone status. Sixty female Wistar rats were fed either a standard diet (n=30) or the same food enriched with IFs (0.87 mg/g of diet) (n=30). After 1 month, they were allowed to mate, and were kept on the same regimen during the whole gestation and lactation periods. At weaning, female pups were each assigned to one of four nutritional groups; within each experimental group, animals were split into two groups, fed either the standard or the IF-rich diet. At 2, 3, 6, 12, 18, and 24 months after birth, 10 animals in each group were sacrificed. Femurs were collected for mechanical testing and bone mineral density (BMD) measurement. The rats perinatally or lifelong exposed to the IF-rich diet exhibited higher body weight and fat mass at 24 months of age. Peak bone mass was achieved between 6 and 12 months and did not differ between groups. In animals perinatally exposed to IF, BMD continued to increase. Thus, at 24 months, femoral total BMD (P<0.05), metaphyseal BMD (P<0.01), and failure load (P<0.05) were higher in the offspring born from mothers provided IF during pregnancy. Postnatal exposure alone did not improve bone parameters. This experiment provides evidence that perinatal exposure to phytoestrogens leads to a higher BMD later in life. It is suggested that these changes may have occurred as a consequence of programming effects, as has been shown for the endocrine and immune systems.

Effect of proximal femoral osteoporosis on cementless hip arthroplasty: A short-term clinical analysis

The aim of this retrospective investigation was to explore the influence of femoral osteoporosis on short-term curative effects of cementless hip arthroplasty and to evaluate the femoral metaphyseal bone mineral density (BMD) for femoral osteoporosis in order to guide prosthesis choice and rehabilitation. We performed 127 total arthroplasty operations between June 1999 to February 2003 and investigated 49 cementless hip replacements with the Metalcancellous cementless Lubeck II system being used in all hips. There were twenty men and twenty-nine women whose mean age at the time of the operation was 60 years (range, 52~81 years). The patients were divided into osteoporosis or normal groups according to the femoral metaphyseal BMD measured preoperatively. The average duration of follow-up was 30 months (range, 8~52 months). We evaluated all of the patients from a clinical standpoint with use of a standard-terminology questionnaire with respect to the short-term curative effects and patients' satisfaction. Hip pain status and functional ability were important indicators of treatment efficacy. Harris hip score and patients' satisfaction in femoral osteoporosis patients who underwent noncemented hip arthroplasty were lower (P=0.004, P=0.03) while the incidence of thigh pain was higher (P=0.03) than the patients with non-osteoporosis. The higher incidence of pain, as well as the decrease in function experienced by the patients in osteoporosis group, supports the case that cementless arthroplasty is not a better choice for those patients and that we had better select prosthesis based on the femoral metaphyseal BMD.

Changes in mineralization and biomechanics of tibial metaphyses in splinted rats

The effect of 3 wk of splintage of a single hindlimb on the midarea and mineral content of both tibial metaphyses was assessed immediately after splint removal and after 1 mo of mobilization in 12-wk-old Sprague-Dawley rats. Immobilization reduced tibial metaphyseal bone mineral density (BMD) in immobilized limbs compared with "free" limbs of splinted animals and with controls. These changes persisted and were accentuated by relatively greater increases in tibial metaphyseal BMDs of unsplinted (control) animals after 7 wk. Immediately after splintage, tibial metaphyseal areas and total mineral contents of both hindlimbs of splinted animals were reduced compared with those of unsplinted animals. However, the relationship between mineralization and area differed between the free and immobilized limbs of splinted animals. The breaking strain and the breaking energy of immobilized and free femurs of splinted animals were impaired 4 wk after the removal of the splint. This impairment was correlated with an effect of splintage on femoral size with some additional local effect from immobilization. Thus osteoporotic changes consequent on immobilization include both local effects on mineralization and general effects on growth, which may separately influence the elastic properties of bone.

Distribution of bone mineral density in the proximal tibia in mid-teens.

The distribution of bone mineral density (BMD) in the proximal tibia was studied in 94 knees from 47 mid-teens. The subjects were healthy high school freshmen (19 male; 28 female) who engaged in daily physical exercise. We measured BMD at six regions of interest (ROI) at the bilateral proximal tibia (three immediately above and three immediately be-low the physeal line) using dual-energy X-ray absorptiometry (QDR-2000; Hologic, Waltham, MA, USA). Subjects were supine during the measurements, with the knee extended and the foot fixed in a special holding device, ensuring correct rotational alignment of the knee. Measurements were performed using the forearm array scan mode. The precision of this method (coefficient of variation) was 1.1%-4.9% (mean 2.5%) for six ROIs. The BMD of the medial side was higher than that of the lateral side, and the BMD at the center of the metaphysis was higher than that of the epiphysis. The subjects in the present study did not show any misalignment of the knee joints. These findings indicate that the medial side of the proximal tibia already has higher BMD than the lateral side in teenagers with normal alignment of the knee joint, and that the increase in epiphyseal BMD may be slower than that of metaphyseal BMD. It is suggested that this phenomenon should be life-long and may play a role in the progression of osteoarthritis of the knee.

Alendronate administration and skeletal response during chronic alcohol intake in the adolescent male rat.

Alendronate is an aminobisphosphonate that inhibits bone resorption in osteoporotic humans and rats but does not induce osteomalacia. Several bisphosphonates, including alendronate, also have direct positive actions on osteoblasts, bone formation, and mineralization. We studied the effects of alendronate on skeletal development in adolescent male rats during chronic alcohol intake. Four groups of age- and weight-matched male Sprague-Dawley rats (35 days of age) were fed the Lieber-DeCarli diet containing 36% of calories as EtOH (E), the EtOH diet plus 60 mg/kg alendronate (EA) every other day intraperitoneally (ip), an isocaloric diet (I), or the isocaloric diet plus 60 mg/kg alendronate (IA) every other day ip. Body weight, femur length, serum levels of osteocalcin (OC), insulin-like growth factor 1 (IGF-1), testosterone, and luteinizing hormone (LH); femur distal metaphyseal and middiaphyseal bone mineral density (BMD) and tibial metaphyseal gene expression for alpha-1-type I collagen (Col I), OC, and bone alkaline phosphatase (AP); and femur strength by four-point bending to failure were measured after 28 days of feeding and alendronate injections. Serum alcohol levels at death were 156 +/- 13 mg/dl (E) and 203 +/- 40 mg/dl (EA). Alendronate given to alcohol-fed rats increased metaphyseal BMD by more than 3-fold over rats fed alcohol alone. Alendronate given to isocaloric pair-fed rats increased metaphyseal BMD by more than 2.5-fold over rats fed the isocaloric diet alone. Cortical BMD was reduced by alcohol but was increased by alendronate. Alcohol consumption reduced serum IGF-1 levels, and alendronate increased IGF-1 levels in alcohol-fed rats. Serum OC, testosterone, and LH were unaffected by alcohol and alendronate. Quantitative dot blot hybridization using rat complementary DNA (cDNA) probes and normalization against 18S subunit ribosomal RNA (rRNA) levels revealed no changes in tibial metaphyseal gene expression for type I collagen, osteocalcin, or alkaline phosphatase. Alcohol significantly reduced the biomechanical properties of the femurs that were partially compensated by alendronate. Chronic alcohol consumption uncouples formation from ongoing resorption, and resorption is inhibited by alendronate. However, alendronate's positive effects on osteoblast-mediated mineralization during chronic alcohol consumption point to the potential use of bisphosphonates in the treatment of decreased bone formation secondary to alcohol-induced diminished osteoblast function.

Bone mineral density at the metaphysis is specifically reduced in STZ-treated diabetic rats

Bone length (L), dry weight (DW) and ash weight (AW) were determined for the femur bone of 9–15 week old female rats with or without streptozotocin (STZ)-treatment. Matrix weight (MW) was obtained by subtracting AW from DW. AW/L 3 and MW/L 3 were taken as measures indicating overall bone mineral density and bone matrix density, respectively. Regional changes such as metaphyseal bone mineral density (MBD) and diaphyseal mineral density (DBD) were determined by single photon absorptiometry (SPA). In the control rats, MW/L 3 and MBD stayed constant in spite of a time-dependent increase in L, whereas the other bone parameters correlated positively with L. Thus MW/L 3 and MBD were compared between rats with different L, and the other parameters were compared with the expected values calculated for L by regression equation. STZ-treatment virtually stopped the growth of L, significantly reduced MBD, but hardly affected MW/L 3. Although DW, AW and AW/L 3 in the STZ-treated rats were significantly smaller than in the control, they were almost identical with the expected values excepting at 6 weeks when the observed values were less than the expected values. DBD in the STZ-treated rats was even larger than the expected values, DW, AW and MBD decreased with time, and MW/L 3 stayed rather constant; only DBD increased time-dependently in these animals. These results suggest that bone mineralization at the metaphysis is specifically reduced in STZ-treated diabetic rats.

Osteopenia in genetically diabetic DB/DB mice and effects of 1alpha-hydroxyvitamin D3 on the osteopenia. Basic Research Group.

To explore the pathogenesis of non-insulin-dependent diabetes mellitus associated osteopenia, we examined age-related changes of the femur metaphyseal bone mineral density in genetically diabetic (db/db) mice and non-diabetic (+/+) mice of the same strain using single photon absorptiometry and characterized the osteopenia pharmacologically and biochemically. Bone mineral density increased with age in the +/+ mice from 5 to 16 weeks of age, but reached a plateau in the db/db mice at 8 weeks of age, and significant differences between the two groups were observed after 12 weeks of age. Ash weight (A) and dry weight (D) of the femur and A/D ratio were significant lower in the db/db mice than in the +/+ mice after 8 weeks of age. Significant elevations of serum calcium and parathyroid hormone (PTH) were observed after 8 weeks and 12 weeks of age, respectively. Serum 1alpha,25-dihydroxyvitamin D levels were significantly decreased in the db/db mice compared to the +/+ mice. Daily oral treatment with 1alpha-hydroxyvitamin D3 (1alpha-(OH)D3) for 4 weeks starting from 8 weeks of age significantly attenuated the bone loss in the db/db mice. These results suggest that an impaired bone mineralization probably by insufficient vitamin D activity and high PTH levels are involved in the osteopenia in the db/db mice. 1alpha-(OH)D3 exerted beneficial effects on the bone loss.

Possible involvement of vitamin D3-deficiency and relatively enhanced bone resorption in the development of bone loss in streptozotocin-induced diabetic rats

To explore the pathogenesis of diabetes associated osteopenia, we characterized the osteopenia in streptozotocin(STZ)-diabetic rats pharmacologically and biochemically. The femur metaphyseal bone mineral density measured by single photon absorptiometry decreased time-dependently in the STZ rats compared with that in control, and the difference reached statistical significance from 2 weeks after treatment with STZ. Closely similar bone loss was obtained in ovariectomized(Ovx) and vitamin D deficient(D(-)) rats. Daily oral treatment with a bone resorption inhibitor, FR78844(a bisphosphonate compound, 100 mg/kg), for 4 weeks significantly attenuated the osteopenia in the STZ and Ovx rats, but not in the D(-) rats, while 1α-hydroxyvitamin D3(1α-(OH)D3) significantly attenuated the osteopenia in the STZ and D(-) rats in a dose of 0.1 μg/kg/day, and that in the Ovx rats in 1 μg/kg/day. The latter dose of 1α-(OH)D3 significantly increased the metaphyseal bone mineral density of the femur in normal rats. Serum levels of 1α, 25-dihydroxyvitamin D(1α, 25-(OH)2D), the most active metabolite of vitamin D, hardly changed in the Ovx rats compared with that in control, but decreased to 24 and 76% that of control in the STZ and D(-) rats, respectively. Serum PTH levels in the STZ, Ovx and D(-) rats were comparable with those in control, but serum calcitonin levels were reduced to 60 and 66% of control in the STZ and Ovx rats, respectively. Serum osteocalcin levels also decreased in the STZ rats compared to control. It is thus speculated that the predominance of bone resorption over bone formation and the reduction of 1α, 25-(OH)2D are involved in the pathogenesis of diabetes associated osteopenia.