Effects of short-term treatment with prednisolone and calcitriol on bone and mineral metabolism in normal men.

To study the effects of treatment with glucocorticoid and calcitriol on biochemical markers of calcium and bone metabolism, 48 normal male volunteers (aged 21-54 years) were randomized to treatment for 7 days with either (A) prednisolone, 10 mg twice daily, (B) prednisolone, 10 mg twice daily, and calcitriol, 1 microg twice daily, (C) calcitriol 1 mg twice daily, or (D) placebo. The study period was 28 days. Renal calcium excretion increased (mean maximal increase +44.7%, p < 0.01) as well as serum parathyroid hormone (PTH) (max. +18.5%, p < 0.01) during prednisolone treatment. Concomitant treatment with calcitriol or calcitriol alone equally enhanced renal calcium excretion (max. +185.2%, p < 0.001) and decreased serum PTH (max. -43.1%, p < 0.001). Prednisolone administration was followed by prompt declines in markers of bone formation [serum osteocalcin (max. -34.7%, p < 0.001) and serum procollagen type I C-terminal propeptide (PICP) (max. -25.9%, p < 0.05)], whereas serum bone alkaline phosphatase (bone AP) remained unchanged. Calcitriol in combination with prednisolone attenuated the decrease in PICP (max. -8.9%, not significant), but it had no effect on osteocalcin (max. -40.1%, p < 0.001), and decreased bone AP (max. -22.2%, p < 0.05). Calcitriol alone increased osteocalcin (max. +37.8%, p < 0.03) and PICP (max. +26.0%, p < 0.05). Among markers of bone degradation, prednisolone suppressed serum C-terminal telopeptide of type I collagen (ICTP) (max. -28.4%, p < 0.001), but not the fasting renal excretion of hydroxyproline (OHP) and collagen type I N-terminal telopeptide (NTx). Calcitriol partially antagonized the decrease in ICTP (max. -17.2%, p < 0.001). Calcitriol alone had no effect on resorptive markers. Extraosseous matrix synthesis was suppressed by prednisolone evaluated by serum procollagen type III N-terminal propeptide (max. -30.8%, p < 0.001) and was not affected by concomitant treatment with calcitriol or calcitriol alone. In conclusion, short-term administration of prednisolone to healthy men leads to fast and protracted suppression of biochemical markers of bone formation and extraosseous connective tissue metabolism. The effect on bone was partially antagonized by simultaneous calcitriol treatment, and points toward a potential role of calcitriol in the prevention of steroid induced osteoporosis.

Meniscal repair by fibrocartilage in the dog: characterization of the repair tissue and the role of vascularity.

Lesions in the avascular part of 20 canine menisci were repaired by implantation of a porous polyurethane. Seven menisci were not repaired and served as controls. The repair tissue was characterized by biochemical and immunological analysis. The role of vascularity in healing was studied by perfusion of menisci with Indian ink. Histologically, repair tissue inside the implants initially consisted of fibrous tissue containing type I collagen. After 2 months, fibrocartilaginous tissue developed inside the implants, whereas control defects only showed repair with fibrous tissue. Both type I and type II collagen, the two major collagen types of normal meniscal fibrocartilage, could be detected in this newly formed fibrocartilage. The implant guided vascular tissue from the periphery towards the lesion resulting in healing of the tear. After fibrocartilage had formed, vascularity decreased and was completely absent in mature fibrocartilage. Control defects remained filled with vascular connective tissue. Two-thirds of the longitudinal lesions were found to be healed partially or completely. It is concluded that implantation of a porous polymer does enhance vascularity sufficiently to result in healing of meniscal lesions extending into the avascular part. Healing takes place by repair tissue strongly resembling normal meniscal fibrocartilage.

Dose-response effect of short-term calcitriol treatment on bone and mineral metabolism in normal males.

To evaluate the effects of short-term treatment with calcitriol on biochemical markers of calcium and bone metabolism, 36 normal male volunteers (aged 21-54 years) were randomized to oral treatment for 7 days with either (A) calcitriol, 1 microgram twice daily, (B) calcitriol, 0.5 microgram twice daily, or (C) placebo twice daily. Serum calcium increased slightly in a dose-dependent manner (maximal increase 2.5%, p < 0.05) followed by a heavy increase in both 24 h (max. 156.1%, p < 0.001) and fasting urinary calcium excretion (max. 123.1%, p < 0.001), and a striking reduction in serum PTH (max. -43.1%, p < 0.001). Biochemical markers of osteoblast activity and bone formation increased immediately in a dose-dependent manner [serum osteocalcin (max. 37.8%, p < 0.03) and serum procollagen type I C-terminal propeptide (PICP) (max. 26.0%, p < 0.05)], whereas there was no effect on serum bone alkaline phosphatase. Calcitriol treatment had no effect on biochemical markers of bone resorption [serum C-terminal telopeptide of type I collagen (ICTP) and fasting urinary excretion of hydroxyproline/creatinine (OHP)]. Extraosseous collagen matrix synthesis was not affected evaluated by serum procollagen type III N-terminal propeptide (PIIINP). In the follow-up period (15 weeks) no unequivocal changes were observed. The fast and protracted increase in biochemical markers of osteoblast activity and bone formation, without affecting bone resorption and extraosseous connective tissue metabolism points toward a selective effect of calcitriol on bone matrix formation.

Meniscal replacement using a porous polymer prosthesis: a preliminary study in the dog.

A porous polyurethane prosthesis was used to replace the lateral meniscus in the dog. After an initial ingrowth of fibrous tissue, the prostheses became filled with tissue strongly resembling normal meniscal fibrocartilage. Although less severe than seen after total meniscectomy, cartilage degeneration was frequent, possibly because tissue ingrowth in the prostheses occurred too slowly. Porous polymers can be useful for replacement of the meniscus, provided that chemical and physical properties are optimized.

Insulin-like growth factor axis, bone and collagen turnover in children with atopic dermatitis treated with topical glucocorticosteroids.

BACKGROUND: Topical glucocorticosteroids are widely used in the treatment of children with atopic dermatitis. Due to percutaneous absorption, these agents may become systemically available and cause inhibition of growth in children. However, the mechanisms responsible for the growth-suppressive effective are not fully understood. OBJECTIVE: To evaluate whether treatment with topical budesonide has any adverse effects on growth-hormone-dependent serum levels of insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein 3 (IGFBP-3), and on the serum markers of bone and collagen turnover osteocalcin, the carboxy-terminal propeptide of type I collagen (PICP), the carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP) and the amino-terminal propeptide of type III procollagen (PIIINP). METHODS: 13 children (mean age 9.5 years) with atopic dermatitis were studied in an open longitudinal trial with run-in and budesonide treatment periods of 2 weeks' duration. During the run-in, only emollient was used. During the treatment period, budesonide cream 0.025% followed by emollient were applied twice daily all over the body except on the face. At day 14 of each period, blood samples were taken and eczema was scored according to a severity index based on extent and activity of the disease. RESULTS: Compared to the run-in, budesonide treatment was associated with a statistically significant reduction in mean severity index (p = 0.002). No statistically significant effects on serum levels of IGF-I, IGFBP-3, osteocalcin or ICTP were observed. The serum concentrations of PICP and PIIINP were reduced with (mean +/- 1 SD) 43 +/- 64 milligrams (95% confidence interval 3.5-80 milligrams, p = 0.03, t = 2.4, d.f. = 12) and 1.2 +/- 1.5 milligrams (95% confidence interval 0.3-2.1 milligrams, p = 0.01, t = 3.0, d.f. = 12), respectively. CONCLUSION: Type I and III collagen turnover may be suppressed during short-term treatment with topical budesonide in children with atopic eczema. clinical implications need further study.

Irradiation of bone metastases in breast cancer patients: a randomized study with 1 year follow-up.

The results from a prospective randomized trial comparing two different radiation schedules for treatment of painful bone metastases in women with recurrent breast cancer are presented. A total of 217 patients with painful bone metastases were randomized to either 30 Grey (Gy) in ten fractions, five fractions a week (5F/W) or 15 Gy in three fractions 2F/W. The effect of treatment was evaluated by pain assessment, the radiological response and the degree of side-effects. The patients were rated at start of treatment and after 1, 3, 6 and 12 months. No difference between the two radiation regimes was found, neither in achieved pain relief, improvement in level of activity and medication, nor was there any difference in radiological response and side-effects from treatment. Both regimes resulted in a significant improvement in both pain score and level of activity 1 month after treatment, an improvement which persisted during the follow-up period. We conclude that 15 Gy given in three fractions 2F/W is as effective as 30 Gy in ten fractions 5F/W, but more convenient to the patient and of less cost to society.

Physical examinations and laboratory tests in antenatal care visits in Denmark. Do reported practice and current official guidelines concord with results of literature reviews? A nationwide study of the public scheme of shared antenatal care in general practice, centres of midwifery and hospital outpatients' clinics.

OBJECTIVE: To analyse physical examinations and laboratory tests reported in antenatal care visits in relation to official guidelines and reviews of appropriateness. DESIGN: A nationwide cross sectional study based on questionnaires completed by general practitioners (GPs), midwives, and hospital doctors. Physical examinations and laboratory tests in connection with one specific visit were reported. SUBJECTS: The questionnaires were completed by 722 GPs (61% of eligible from a random sample), 584 midwives (86% of eligible), 250 hospital doctors who made health examinations in pregnancy, week 16-18 (63% of eligible), and 181 hospital doctors who saw women with at-risk pregnancies (55% of eligible). RESULTS: General practice: weight, blood pressure (BP) measurement, and test for proteinuria were reported in more than 90% of visits. Urine culture was reported in 46%, and cervical smear in 41% of first visits. Rubella antibody test at the first visit was only reported in 23% of nulliparae. Vaginal examination was reported in 95% of first visits. Fewer were reported in second (27%) and third (48%) routine visits during pregnancy. Midwives: checks of BP, oedema, and proteinuria were reported in more than 95% of visits irrespective of week of gestation. Vaginal examination was reported in about a third of checkups. Hospitals: vaginal examination was reported in 66% of checkups in at-risk pregnancies. CONCLUSIONS: A surplus of resources were spent on (repeat) examinations and tests with little or no documented benefit. Cervical cytology was grossly overused. Urine culture and rubella serology were not sufficiently applied.

[Preventive health examinations of pregnant women in Denmark. Anamnestic practice and discussion of prenatal diagnosis in early pregnancy examinations in general practice, birth clinics and birthing centers]. / Forebyggende helbredsundersøgelser af gravide kvinder i Danmark. Anamnesepraksis og samtale om proenatal diagnostik ved tidlig undersøgelse i svangerskabet hos praktiserende loege, på fødestedet og hos jordemoder.

In Denmark, pregnant women are offered antenatal care in a nationwide programme. This programme is organized around health examinations in general practice, hospital outpatient departments and at midwives' centres. During winter 1986-1987, a nationwide investigation of antenatal care was carried out. A random sample of approximately 1/3 of the general practitioners, all of the midwives who had antenatal consultations and the medical staffs of 26 departments of obstetrics and gynaecology received a questionnaire about content of a definite antenatal examination. 62% of the general practitioners, 63% of the doctors at the place of delivery and 86% of the midwives replied. Among the pregnant women, 92% replied from general practice, 84% from hospital outpatient departments and 91% from midwives' centres. The interviews about date of delivery and genetic counselling at early visits in general practice, hospital outpatient departments and at midwives' centres were in agreement with the nationwide guidelines. Employment of routine ultrasound scanning was not associated with less detailed history taking by the doctors at hospital outpatient departments, where ultrasound scanning was employed only on special indications. It was concluded that there was a considerable overlap between the interview about the date of delivery and genetic counselling at early visits in general practice and in hospital outpatient departments and, to some extent, at the midwives' centres. The sharing of responsibility for care of pregnant women by three professional groups requires specification of the content of the consultation. Official guidelines should be more specific about this point.

Plasma thromboxane B2 as an early marker of acute graft rejection after heart transplantation: preliminary report.

Six patients undergoing heart transplantation were followed up by serial endomyocardial biopsies to detect signs of graft rejection and the plasma level of thromboxane B2 was measured at the same time. During the operative procedure and concomitant with histologic signs of acute graft rejection, the plasma level of thromboxane B2 significantly increased. After immunosuppressive treatment with steroids and either antithymocyte globulin or monoclonal antibody, regression of the histologic signs of rejection and a significant fall in the level of thromboxane B2 were documented. We conclude that the plasma level of thromboxane B2 may be useful as an early marker of acute graft rejection after heart transplantation.

[Satisfactory results of shelf arthroplasty in hip dysplasia and in dysplasia with arthritis]. / Goede resultaten van pandakplastiek wegens heupdysplasie en dysplasie met artrose.

Between 1969 and 1987, 30 shelf arthroplasties were performed in 28 patients for the treatment of dysplasia and dysplastic arthrosis of the hip in the Department of Orthopaedic Surgery at the University Hospital of Groningen. Twenty-two patients, of whom 2 were treated bilaterally, were free of complaints after a mean follow-up period of 7.25 years (2-20 years). Twenty-three cases could be classified as clinically successful and 19 of the 30 as radiologically successful. The shelf operation is a safe and relatively simple procedure and for cases of acetabular dysplasia creates a better situation for total hip replacement in later life.

Comparison of calcium carbonate and aluminium hydroxide as phosphate binders on biochemical bone markers, PTH(1-84), and bone mineral content in dialysis patients.

Bone mineral content, estimated by single-photon absorptiometry of the forearm, serum values of intact parathyroid hormone (PTH(1-84], osteocalcin, alkaline phosphatase, 1,25-dihydroxycholecalciferol (1,25(OH)2D3), and aluminium were determined during treatment with calcium carbonate (CaCO3) or aluminium hydroxide (Al(OH)3) in 11 dialysis patients participating in a randomised cross-over study. Each treatment period lasted 6 months. Serum phosphorus was maintained in the range 1.5-2.0 mmol/l. During Al(OH)3 treatment bone mineral content (BMC) decreased by 11% per half-year (mean), but only by 3% per half-year during CaCO3 treatment (P less than 0.05). Comparing the CaCO3 and Al(OH)3 periods the following differences were found: serum calcium increased during CaCO3 treatment, PTH(1-84) decreased (79% of initial values during CaCO3 versus 196% during Al(OH)3, mean area under curve, P less than 0.05), osteocalcin decreased (89% versus 117%, P less than 0.01), alkaline phosphatase decreased (92% versus 116%, P less than 0.05), and aluminium decreased (56% versus 189%, P less than 0.05). 1,25(OH)2D3 remained unchanged in both periods. No increase in soft-tissue calcification was demonstrated on X-ray of the shoulders in any of the periods. Thus, CaCO3 treatment seems to slow down loss of bone mineral content, and using CaCO3 as phosphate binder may have a more beneficial effect on the progression of uraemic bone disease than Al(OH)3 due to the reduction of hyperparathyroidism and bone turnover.

Pathophysiology of venous thromboembolism.

Venous thromboembolism is complex with a multifactorial etiology. The Virchow triad (changes in blood flow, changes in vessel wall, and changes in the properties of blood) gives the main factors involved in venous thromboembolism. Venous stasis during immobilization in general anesthesia, stroke with hemiparesis, and heart failure plays a central role. The thromboembolic process can be initiated by a disturbance in the normal "hemostatic balance," with an increased thrombogenic potential, due to release of thromboplastin and collagen exposure during vessel wall injury by stasis and hypoxia, decreased fibrinolysis during surgery, malignancy, among others. Many substances modify these processes, including heparan sulfate, AT III, protein C, t-PA inhibitor, and alpha 2-antiplasmin.

Diurnal rhythm and 24-hour integrated concentrations of serum osteocalcin in normals: influence of age, sex, season, and smoking habits.

In the present study we examined whether the diurnal pattern and the 24-hour integrated serum concentration of osteocalcin (S-OC(I] showed any variation due to age, sex, season, or smoking habits in 31 normal subjects, aged 23-47 years. Blood samples were drawn every 60 minutes from 4 p.m. until 6 p.m. the following day. Serum osteocalcin showed diurnal variation as described earlier but no influence of age or sex on the diurnal variation could be demonstrated. Ten subjects were smokers, all consuming more than 10 cigarettes daily, but the diurnal variation in OC with time was not different from an age-, sex-, and height-matched group of strictly nonsmokers. Sixteen of the subjects were initially examined in March and 15 in November. Eight subjects were examined during a period in both November and March, and 5 of these went through an additional study period in July. These seasonal studies showed that the diurnal time course pattern during different seasons of the year were statistically indistinguishable from each other. The S-OC(I) was significantly higher in subjects below 29 years of age compared with subjects aged 30-40 years (P less than 0.01). Men had higher values than women (P less than 0.05). Moreover, S-OC(I) was higher in November compared to March (P less than 0.05). There was no effect of smoking on S-OC(I). A significant correlation existed between S-OC(I) and age (r = 0.50, P less than 0.005). Multiple regression showed that among age, height, and weight, only age and height were significant determinants for S-OC(I) (r = 0.50, P = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

[Long-term results of the Swanson prosthesis for the treatment of lunate osteomalacia]. / Lange-termijnresultaten van de Swanson-prothese ter behandeling van lunatomalacie.

From 1972 to 1982 a silicone implant arthroplasty was performed in 18 patients with Kienböck's disease grade III. In May 1988 all patients had a clinical and radiological re-examination. In the course of time reoperations were performed in 4 patients because of (sub)luxation of the prosthesis. Because of this operation most of the patients had less pain and retained an acceptable function of the wrist. Influence on working circumstances had been considerable in 8 patients. One patient received a disability pension because of this disease. Radiological examination often revealed increased degenerative changes in carpo-radial and intercarpal joints as well as proximal migration of the capitate. There was no clear relationship between residual complaints and function at the follow-up examination and the radiological findings.

Changes in biochemical markers of osteoblastic activity during the menstrual cycle.

Serum levels of osteocalcin [OC; bone Gla protein (BGP)] and bone alkaline phosphatase (B-AP) are both correlated to osteoblastic activity, which may be regulated by several hormones, including estrogen, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], and PTH. Estrogen shows reproducible variations during the menstrual cycle, while available data on variations in serum 1,25-(OH)2D3 and serum immunoreactive PTH show midcyclic increases or no changes. In the present study we evaluated osteoblastic activity by measuring serum OC and B-AP during the menstrual cycle in eight healthy women, aged 20-47 yr. The cycles were synchronized by LH peaks, and follicular and luteal periods were normalized by lengths. Repeated measures analysis of variance showed that serum OC varied significantly (P less than 0.05), with highest levels during the luteal period. Although the same pattern was seen for serum B-AP, the variation just failed to reach significance (P less than 0.10), but the mean level was significantly higher during the luteal than during the follicular period (P less than 0.05). Gonadotropins and ovarian sex hormones showed significant variations. There were no significant changes in serum vitamin D-binding protein, serum total and free 1,25-(OH)2D3 index, or serum immunoreactive PTH-(1-84), but serum levels of somatomedin-C showed a significant variation, with the highest level during the luteal period (P less than 0.05). Blood levels and urinary excretion of minerals exhibited no significant variations. Cross-correlation studies between OC and estradiol showed the highest correlation coefficient, when OC was lagged about 7 days after estradiol (r = 0.69; P less than 0.05). Moreover, a high correlation was found between OC and somatomedin-C when matched at concurrent time points (r = 0.76; P less than 0.01). No significant correlations were found between the other calcium-regulating hormones and OC when matched at concurrent time points. In conclusion, we found a significant effect of the menstrual cycle on the serum levels of two osteoblastic bone markers, OC and B-AP. The changes indicated that osteoblastic activity is higher during the luteal period. However, whether the changes are caused by direct or indirect effects of the fluctuations in calciotropic hormones is still unresolved.

An extendable modular endoprosthetic system for bone tumour management in the leg.

A modular endoprosthetic system has been developed at the Groningen University Hospital and the University of Twente. The system can bridge a defect resulting from the resection of a malignant bone tumour which has developed around the knee joint of a child. Since the other healthy leg continues to grow, the system includes an element whose length can be adjusted non-invasively by using an external magnetic field. In addition to this lengthening element, there are one hip and two knee components, connectors of various lengths, and fixation elements. The paper describes the elements of the modular endoprosthetic system. Tables are created by means of which the elemental composition of such an endoprosthesis can be determined for each individual patient.

Pigmented villonodular synovitis.

Pigmented villonodular synovitis is a benign disease of the synovial membrane of joints, tendon sheaths, or bursae, which nevertheless can cause marked local destruction. Its diagnosis is often delayed because complaints and symptoms are nonspecific. Familiarity with the disease may ensure an earlier diagnosis and consequently early onset of therapy, which may prevent serious damage. This paper describes 18 patients suffering from localized or diffuse pigmented villonodular synovitis. Findings possibly suggestive of pigmented villonodular synovitis include hemarthrosis, soft tissue swelling, radiological evidence of cyst formation at a distance from the weight-bearing area of a joint, an increased triglyceride concentration, and a positive bone scan. A normal appearance on arthroscopy does not rule out the disease. Therapeutic results are better in the localized than in the diffuse form of the disease.

[Osteoid osteoma and osteoblastoma]. / Het osteoïde osteoom en het osteoblastoom.

A follow-up study, based on clinical, radiological and pathological information was performed of 20 patients who had suffered from an osteoid osteoma and of three patients who had been treated for an osteoblastoma in the period 1978-1988. 50% of the patients mentioned both pain at night and a good reaction to salicylates. In 87% of the cases a correct diagnosis was made with the aid of conventional radiography, tomography and bone scanning. Primary treatment consisted of intracapsular (mostly piecemeal) excision in all cases. A local recurrence was observed in one patient with osteoid osteoma and in two with osteoblastoma. At the time of this follow-up study none of the 23 patients had complaints. Histopathological examination did not reveal any difference between the two types of bone tumour.