Serum bone-gla protein after fracture

Serum bone Gamma-carboxyglutamic acid (bone-gla) protein (BGP), a marker of bone formation, was measured in serial blood samples drawn from 14 patients who had fractured at least one of their tibial or femoral diaphyses and from two other patients who had sustained major trauma without fracture but who had been immobilized. A total of 85 samples were taken and analyzed during the first three months after the fractures occurred. Serum BGP significantly increased and positively correlated with the time that had elapsed after the fracture, with an average twofold increase after two months. The fracture site and the duration of immobilization had no influence on the serum BGP levels. Serum BGP levels from the two non-fractured cases increased in the first two weeks with no subsequent consistent trend. These data suggest that serum BGP increases one to two months after a major fracture, possibly as a manifestation of bone repair. Further studies are required to determine the potential clinical value of serum BGP in the management of such patients.     

Effects of Clodronate on Cortical and Trabecular Bone in Ovariectomized Rats on a Low Calcium Diet

The aim of this study was to evaluate the contribution of a low calcium diet to the cortical and trabecular osteoporosis seen in ovariectomized rats after 7 weeks on a low calcium diet and to investigate the effects of the bisphosphonate clodronate on this development of osteoporosis. Thirty-six mature, female Wistar rats were randomized into four groups: Ovx−B (bisphosphonate) and Ovx−C (control) were ovariectomized, and Sham−Ca (low calcium) and Sham+Ca (normal calcium) were sham operated. The first three groups were fed a low calcium diet (0.01%) and Sham+Ca normal rat chow (Ca 1.1%). The Ovx−B received 10 mg/kg s.c. clodronate daily for nine weeks, and Ovx−C, Sham−Ca, and Sham+Ca received the same volumes of saline. Bone mineral turnover measured as ⁸⁵Sr-uptake was increased in all low calcium groups compared to Sham+Ca. The Sham+Ca femora had higher dry weight and ash weight than the other groups, and Ovx−C had higher dry weight compared with Ovx−B and Sham−Ca. Calcium content was lower in both Ovx groups compared to both Sham groups. Magnesium was lower in all groups compared to Sham+Ca and higher in Ovx−B compared with Ovx−C. In the femoral shaft, Sham+Ca had significantly higher ultimate bending moment, energy absorption, and deflection compared to the other three groups. Ultimate bending moment was higher in Sham−Ca than in Ovx−C. Stiffness was increased in both Sham+Ca and Ovx−B compared to Ovx−C. The maximum stress in the femoral midshaft was higher in Sham+Ca than in the other groups, and higher in Ovx−B than in Ovx−C. Histomorphometry showed increased medullary area in all low calcium groups compared to Sham+Ca and larger cortical area in Sham+Ca and Ovx−B compared to Ovx−C. Compared to Sham+Ca the trabecular bone volume was decreased to 30% in Sham−Ca and to 9% in Ovx−C, but was unchanged in Ovx−B. The low calcium diet generally increased bone mineral turnover and reduced the tibial bone volume. Femoral changes led to a reduction of cortical fracture strength and maximal stress. Ovariectomy in addition to a low calcium diet reduced femoral strength even more. Daily injections of clodronate to ovariectomized rats on a low calcium diet increased femoral shaft stiffness and maximum stress, and clodronate preserved both trabecular and cortical tibial bone volume completely. Received: 11 June 1996 / Accepted: 5 March 1997     

Single Nucleotide Polymorphisms in the Human Gene for Osteoprotegerin are Not Related to Bone Mineral Density or Fracture in Elderly Women

Osteoprotegerin (OPG), a secreted member of the tumor necrosis factor receptor family, is a potent inhibitor of osteoclast activation and differentiation. In animal models OPG prevents bone loss, and in humans bone resorption can be reduced by injections of OPG. OPG may also play a role in cardiovascular disease since mice lacking the OPG gene display arterial calcification. In a screening effort of the OPG gene, we recently discovered a single nucleotide polymorphism in the promoter region of OPG (T950C), and reported an association with vascular morphology and function in 59 healthy individuals. Due to the pronounced effect of OPG on bone turnover, the present study was conducted to investigate whether OPG polymorphisms are also associated with bone mineral density or with fracture. The relationship between single nucleotide polymorphisms in the promoter region of OPG (T950C) and the first intron (C1217T), and bone mineral density, measured by DXA in the hip or spine or ultrasound of the heel, was investigated in the Malmö OPRA-study of 1044 women, all 75 years old. The possible relation to fracture incidence was also analyzed. Among the 858 and 864 individuals respectively, genotyped, no significant associations between the investigated single nucleotide polymorphisms and bone mineral density measurements (T950C P = 0.50–0.64, C1217T P = 0.51–1.00), quantitative ultrasound measurements of the calcaneus, or fractures (T950C P = 0.61–0.66, C1217T P = 0.14–0.33) were found. Thus, our results show that polymorphisms in the OPG gene, one of which has previously been found to be associated with cardiovascular morphology and function, are not associated with bone mineral density in elderly Swedish women.     

Impairment of bone turnover in elderly women with hip fracture

Summary Hip fracture is one of the most severe consequences of osteoporosis affecting aged women. However, abnormalities of bone turnover responsible for bone loss in this condition have not been clearly defined. To further evaluate the bone metabolic status of women sustaining hip fracture, we have prospectively measured serum osteocalcin as a marker of bone formation and urinary excretion of pyridinoline (Pyr) and deoxypyridinoline (D-pyr) cross-links as markers of bone collagen degradation in 174 independently living women (80 ± 8 years) within a few hours after a hip fracture. Comparison was made with 77 age-matched controls (80 ± 5 years) and 17 premenopausal women (39 ± 3 years). In addition 15 of the patients were followed with daily measurements during the first postoperative week. At the time of admission osteocalcin was 20% lower in the fractured women compared to the elderly controls (7.6 ± 3.8 vs. 9.5 ± 4.5 nglml,P = 0.001). Pyr and D-pyr were 36% and 40% higher, respectively (P = 0.0001), than in elderly controls and 85% and 76% higher than in premenopausal controls (P = 0.0001). Serum osteocalcin did not correlate with the cortisol level measured at the same time (r = 0.03, ns), nor with serum albumin and creatinine. Serum osteocalcin remained unchanged within 18 hours after fracture, whereafter it progressively decreased until the third postoperative day. No correlation was noted between the excretion of pyridinoline cross-links and the time elapsed from fracture.These data suggest that the abnormal levels of osteocalcin and pyridinolines are unrelated to traumatically induced acute changes, but reflect abnormalities of bone turnover existing prior to the fracture. Thus, hip-fracture patients have biochemical evidence of decreased bone formation and increased bone resorption when compared to age-matched controls. We suggest that these abnormalities may play a role in the decrease of the bone mass and the consequently increased bone fragility that characterize the osteoporotic hip fracture in the elderly.     

Estrogen-progestogen therapy for low bone mineral density in primary biliary cirrhosis

Abstract: Aims/Background: Patients with primary biliary cirrhosis (PBC) often have osteoporosis of the high-turnover type, suggesting that estrogen could have a beneficial effect. However, the cholestatic potential of estrogen could imply a risk of increased cholestasis in a disease characterized by cholestasis. The aim of the present study was to test whether hormone replacement therapy (HRT) could be used to increase bone mineral density (BMD) in PBC patients with osteoporosis, without causing deterioration of the liver function. Methods: Nine female PBC patients with osteoporosis and one with osteopenia were offered HRT for two years. The change in BMD was compared to the change in ten age-matched female PBC patients who had less severe or no osteopenia and who did not receive HRT. Liver function tests were checked at six-month intervals. Results: HRT patients showed a statistically significant increase in lumbar spine BMD and total body BMD whereas control patients showed a significant decrease in lumbar and total body BMD. In contrast to the controls, HRT patients also showed a decrease in truncal fat (–3.8%). Neither of the groups showed any statistically significant changes in the liver function tests. Conclusions: HRT is safe and effective in female PBC patients with osteoporosis.     

Changes in the testis parenchyma caused by acute nonspecific epididymitis

22 patients, hospitalized for observation and treatment of acute nonspecific epididymitis, participated in a study designed to examine the extent of infective involvement of the testicular parenchyma in conjunction with acute nonspecific inflammation in the epididymis. An attempt was made in a followup to classify possible injury to spermatogenesis occurring after nonspecific epididymitis. Age at onset of acute nonspecific epididymitis varied between 21-82 years. The epididymitis was unilateral in 20 patients and bilateral in 2 patients. 12 patients had symptoms of posterior urethritis. 18 patients were followed for 2-3 years after the acute onset. 3 of the older patients had died of intercurrent diseases at the time of the followup. Aspiration biopsy from the testis was performed with a 23-gauge needle; punctures were carried out during short-term narcosis 4-15 days (average 7 days) after the onset of the epididymitis. A section biopsy of testicular parenchyma was taken for histopathologic examination in 4 patients. Bacteriologic cultivation of the urine was performed in all 22 patients, and a portion of the aspirated material at testis puncture was sent for bacteriologic examination in 11 patients. The followup examination included palpation of the testes, at which time turgidity and consistency on both sides were judged. Atrophy of the testis is defined as a difference in consistency, as well as in size, between the affected and the healthy sides. Testicular atrophy was considered to be present if the combined axis measurements for the 2 sides differed by 10 mm or more and if the consistency of the testes differed. 16 of the patients showed an inflammatory cell reaction in the testis; a reduction of spermatogenesis was observed in the same number of cases. There was a significant correlation between the degree of the inflammatory cell reactions and the reduction of spermatogenesis. The 9 patients who showed a pronounced inflammatory cell reaction all had marked reduction of spermatogenesis. Of the 18 followup patients, 12 showed atrophy. Both of the bilateral caseds were among these. 6 patients were judged to have clinically normal testes. There was significant correlation between the presence of atrophy 2-3 years after the episode of acute epididymitis and the degree of inflammatory cell reaction during the acute infection phase. Of the 8 patients who showed pronounced inflammatory cell reactions, atrophy of the testis was found later in 7; 4 of the patients who did not show any inflammatory cell reactions had normal testis size and turgidity.     

Comparing ultrasonography, magnetic resonance imaging and scintigraphy in evaluating an experimentally induced muscular hematoma

A standardized trauma was inflicted to the lateral side of the calf muscle of 12 New Zealand rabbits, creating a muscle hematoma without external bleeding. The acute hematoma was evaluated within 3 h with radionuclide imaging of red blood cells labelled with ^99mTc pertechnetate, ultrasonography and magnetic resonance imaging (MRI). The results were compared with the total volume of the hematomas as calculated from histological preparations of each injured muscle. Scintigraphy and T2-weighted MRI accurately detected all hematomas but the calculated volume did not significantly correlate with histology. T1-weighted MRI did not detect the hematomas. Ultrasonography detected all hematomas and also accurately evaluated the volume. In conclusion, scintigraphy, MR imaging and ultrasonography are all sensitive enough to detect an acute muscle injury, but in this investigation only ultrasonography accurately quantified the volume of the hematoma.     

Electron microprobe analysis and histochemical examination of the calcium distribution in human bone trabeculae: a methodological study using biopsy specimens from post-traumatic osteopenia

Energy dispersive X-ray microanalysis (EDX) (or electron microprobe analysis) of the relative intensity for calcium in different bone trabeculae from the tibia epiphysis, and in different parts of one and the same trabecula, was performed on 3 patients who had earlier had a fracture of the ipsilateral tibia-diaphysis. The variation in intensity was compared with the histochemical patterns obtained with both the Goldner and the von Kóssa staining techniques for detecting calcium in tissues. Previously reported calcium distribution features, found to be typical for posttraumatic osteopenia, such as striated mineralization patterns in individual trabeculae and large differences in mineralization level between different trabeculae, could be verified both by means of the two histochemical procedures and from the electron microprobe analysis. A pronounced difference was observed, however, between the two histochemical staining techniques as regards their sensitivity to detect calcium. The two methods have different turnover points, from negative to positive along a gradient change of calcium concentrations. To judge from the values obtained from the EDX measurements, the sensitivity of the Goldner technique should be more than ten times higher than that of von Kóssa. The EDX measurements gave more detailed information than either of the two histochemical techniques: great variations in the intensity of the calcium peak were found in trabeculae stained as unmineralized as well as mineralized.