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The genotoxicity of fluoride in vivo in seven patients with osteoporosis was cytogenetically investigated. The patients were treated with fluoride-containing formulations (disodium monofluorophosphate and sodium fluoride) for a period of 15 months up to 49 months. Fluoride intake ranged from 22.6-33.9 mg F/day and serum fluoride concentrations were between 0.1 mg F/l and 0.2 mg F/l. Peripheral blood lymphocytes of these patients were cultured in vitro and examined for chromosomal aberrations, micronuclei in cytokinesis-blocked binucleated lymphocytes as well as cell cycle progression. When a comparison was made between patients' group and a matched control group, it was found that fluoride at the tested concentrations had no detectable genotoxic potential in human.

The absolute bioavailability and other pharmacokinetic parameters of two fluoride formulations were investigated in 13 healthy volunteers, aged 61-70 years.The following formulations were administered, under fasting conditions, in a single-dose three-way cross-over design: tablets of 76 mg disodium monofluoro phosphate (MFP, equivalent to 10.0 mg F- ion), enteric-coated (e.c.) tablets of 25 mg sodium fluoride (NaFor, equivalent of 11.3 mg F- ion), and an isoosmotic aqueous injection solution (4 ml) of 22.1 mg sodium fluoride (NaFiv, equivalent of 10.0 mg F- ion). There was a wash-out period of at least one week between each administration. Blood was sampled before and during a 24-hour period after administration. For F- excretion urine was sampled 48 hours before (baseline) and over the 48 hours after the administration.The mean t1/2 values of the three formulations were 8.3, 8.7 and 8.3 h for MFP, NaFor and NaFiv respectively, and were not significant different. Mean Cmax after MFP was significantly higher than after NaFor [344 vs 142 micrograms.l-1]. Mean tmax for MFP was shorter than for NaFor [1.1 vs 4.6 h]. MFP had significantly higher bioavailability [102.8%] than NaFor [64.2%].The MFP formulation showed higher bioavailability with smaller variation than the NaFor formulation. MFP is preferable, therefore, for fluoride therapy in clinical practice, and changing from NaFor to MFP will require adjustment of the dose.

Specific binding to and proliferative actions of insulinlike growth factors-I and -II (IGF-I and -II) on fetal mouse osteoblasts were tested. Membranes of mouse osteoblasts were shown by binding competition studies to possess specific binding sites for IGF-I and IGF-II. When IGF-I was used as a tracer, half-maximal displacement was obtained with 1·11 μg IGF-I/1 and with 14 μg IGF-II/1. Displacement of 125I-labelled IGF-I was accomplished with 2·33 μg IGF-II/1 and with 55 μg IGF-I/1. Affinity cross-linking showed bands of 130 kDa 125I-labelled IGF-I and 260 kDa 125I-labelled IGF-II under reducing conditions, further indicating the presence of classical type-I and -II receptor sites on mouse osteoblasts. Mitogenic effects of IGFs were weak; a combination with epidermal growth factor or fibroblast growth factor showed strong synergistic action however. The possibility of autocrine/paracrine actions of IGFs is discussed. Journal of Endocrinology (1990) 125, 271-277

The reproducibility and diagnostic value of local bone to soft tissue uptake ratio of99mTc(Sn)-MDP as a bone tracer was examined in a prospective study in 35 patients who were under investigation and/or treatment for postmenopausal osteoporosis. The ratio of tracer uptake in the second lumbar vertebra (L2) and both femoral shafts was calculated from the number of counts in suitable regions of interest. Results obtained with settings and calculations in the routine practice were compared to the results obtained by revision of all raw data in one run by one person. The results were compared to the serum alkaline phosphatase activity (AP) and to local bone mineral mass as determined by dual photon absorptiometry (DPA). In 15 patients serial measurements during fluoride therapy were also compared to serum osteocalcin values and to bone histomorphomatric data. The precision error of the calculation of uptake ratios from raw counts (including selection of region of interest) was 13.9% for the femoral shaft and 14.7% for L2. The mean difference between left and right femoral shaft in individuals was not significant and its variance was smallP > 0.1). There was a weak but significant linear correlation between local uptake ratio in the spine and AP in the total material (r=0.328P < 0.01). However, changes in local uptake ratio during therapy with fluoride in 15 patients were too small to be of any value and did not correlate with changes in alkaline phosphatase or osteocalcin or trabecular surface covered with osteoblasts. We conclude therefore that local uptake ratio of bone seeking isotopes has no value in assessing general metabolic bone activity in osteoportic patients, for diagnostic purposes or in the follow up of their response to therapy, except for the detection of local untoward reactions.

For the objective assessment of the severity and progression of osteoporotic deformities of the spine, a mathematical model has been developed which permits evaluation of a single set of radiographs of the spine without reference to absolute values of vertebral height. The model was based on measurements of anterior, central and posterior heights of the vertebrae Th4 to L5 of 50 subjects, aged 20 to 50 years, without a history or radiologic signs of osteoporosis or other metabolic bone disease and without traumatic deformities. The model follows a simple sinusoidal function which describes the general form of the spine, adapted to the individual's height and build. A spine fracture index (SFI) is produced and the method allows calculation of the total number of vertebral deforming events (VDE), and vertebral deformation score (VDS) in an objective manner. The method has been used prospectively in 178 spine radiographs of 109 subjects (60 healthy early postmenopausal women and 49 with osteoporosis). Sensitivity and specificity of SFI in identifying osteoporotic patients were 94 and 88% respectively. In all 109 persons, densitometry of the spine was performed by dual photon absorptiometry at the same time. In the osteoporotic patients the examination was repeated once or twice during fluoride therapy for osteoporosis. The SFI and the total score of VDE and VDS correlated significantly with lumbar bone mineral content (r = -0.38 P < 0.001). The method offers the advantage of being objective, not dependent on projection errors, and adaptable to the shape of the individual spine.

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

Stoornissen in mobiliteit en lichaamsbalans door slechter kunnen bewegen en/of verlies aan sturing en aan initiatief leiden tot afhankelijkheid en hebben psychosociale gevolgen. De ernst is vaak al door anamnese vast te stellen.

Vitamin D deficiency may lead to loss of type II muscle fibres, and thereby to atrophy of proximal muscles with an increased risk of falling and bone fractures. The aim of the study was to determine if six months of vitamin D treatment (0.5 microg alphacalcidol) could positively influence values for muscle strength and functional mobility in vitamin D-deficient older women. Twenty-seven women entered the study which took place at a teaching hospital outpatient department. Ten vitamin D-deficient (serum 25(OH)D320 nmol/L) older (70 years) women and 13 age-matched female subjects with normal vitamin D levels (serum 25(OH)D330 nmol/L) completed the study. Preand post-treatment data were obtained for isometric knee extensor strength, handgrip strength and functional mobility (walking distance over 2 minutes and the timed i'UpGo" test). Six months of treatment with alphacalcidol led to significant improvements (compared to the controls) in values of isometric knee extensor strength (left leg: 14.6% +/- 5.7%. p=0.03; right leg: 11.5% +/- 5.0%, p=0.02) (mean +/- SEM). The achievements in the timed "UpGo" test and 2-minute walking test did not improve in the alphacalcidol group compared to the controls after 6 months. However, within the vitamin D-deficient group, 6 months of alphacalcidol treatment led to a significant increase in the walking distance over 2 minutes (increase from 137.6 +/- 12.6 to 151.3 +/- 11.2 meters, p=0.03). The controls, with normal vitamin D levels, did not exhibit improvements in performance of any of the tests over a period of 6 months. Summarized, alphacalcidol seems to improve muscle strength and walking distance over 2 minutes in vitamin D-deficient older women.

The Dutch College of General Practitioners published well documented guidelines for the management of osteoporosis. It is however incorrect to use the Z-score for the elderly and the T-score for other age groups. The guidelines balance the patient's and the physician's interests and the financial consequences of osteoporosis. They demand certainty about recommending the GP's interventions and accept less certainty where the influence on the GP's activities is limited. The guidelines contain weighed judgements by and for GP's; it is questionable whether they are adequate regarding the interaction with the increasingly well informed patient.

The genotoxicity of fluoride in vivo in seven patients with osteoporosis was cytogenetically investigated. The patients were treated with fluoride-containing formulations (disodium monofluorophosphate and sodium fluoride) for a period of 15 months up to 49 months. Fluoride intake ranged from 22.6-33.9 mg F/day and serum fluoride concentrations were between 0.1 mg F/l and 0.2 mg F/l. Peripheral blood lymphocytes of these patients were cultured in vitro and examined for chromosomal aberrations, micronuclei in cytokinesis-blocked binucleated lymphocytes as well as cell cycle progression. When a comparison was made between patients' group and a matched control group, it was found that fluoride at the tested concentrations had no detectable genotoxic potential in human.

In three patients, two men aged 84 and 80, and a women aged 88, physicians had advised against further diagnostic examination or treatment, mainly because of the advanced age. One of the patients was not satisfied with his deterioration and asked for further examination, the other two were brought to the hospital by relatives in order to be further examined. In all three cases, additional investigation revealed treatable disorders (Crohn's disease, depressive disorder and complications of Parkinson's disease). It is argued that very old age as such is not a sufficient reason to refrain from further diagnostic investigation or treatment. Sufficient reasons are (a) certainty with respect to the diagnosis, (b) knowledge of technical aspects of diagnosis and treatment, notably regarding potential yield and stress for the patient, and (c) approval by the patient, his representative or family members.

To study the appropriateness of minimally invasive surgical treatment of primary hyperparathyroidism.Prospective.University Hospital Utrecht, the Netherlands.In patients with primary hyperparathyroidism, parathyroid adenomas were located preoperatively by means of Doppler assisted ultrasonography and spiral computer tomography. If the results were positive, minimally invasive surgery was performed.Minimally invasive surgery was carried out in 13 out of 15 successive patients with good results (the serum calcium and parathyroid hormone levels returned to normal). Two patients were subjected to conventional neck exploration, also with good results (preoperatively several adenomas were suspected in one, while no adenoma was seen in the other).It can be calculated that minimally invasive surgery will probably suffice in 60-70% of the patients with primary hyperparathyroidism, so that conventional neck exploration can be avoided.

The purpose of this study was to examine the effect of patient- and non-patient-related factors (co-morbidity, demographics, and method of surveillance) on the frequency of "do-not-resuscitate" (DNR) orders in aged inpatients.On a geriatric ward, during three different periods within 1 year, we used two different methods of data collection (with or without a form) and two different time-frames (prevalence or incidence) in studying the frequency of DNR orders, demographic data and the Pre-Arrest Morbidity (PAM) Index.In a sample of 261 patients the DNR decision was related to patient-related factors, including the PAM score and age. Only 3 patients with a score above 4 had no DNR order and in the group of 142 patients83 years 85 (59.9%) had a DNR order, compared to 52 (43.7%) of the 119 patients of 83 years or less (p0.05). In contrast, gender and marital status were not related to the presence of a DNR order. The variables PAM score, age, form and time-frame classified 76.6% of the cardiopulmonary resuscitation (CPR) decisions correctly and 71.5% of the DNR decisions correctly. Without attention to the resuscitation decision, the written DNR order frequency decreased significantly from 64-59% to 23%. An explanation for this variance may be the passive process of data collection, a non-patient-related factor.The DNR decision is related to the PAM index score and age. The variance in DNR decisions is partly related to the method of data collection, a non-patient-related factor in DNR decision-making. Without attention to the DNR/CPR decision, the DNR frequency decreased markedly.

The use of 'do not resuscitate' (DNR) orders was analysed on a Dutch geriatric ward for a 4-month period. Of 148 admissions, 68 (58%) received a written DNR order. The use of DNR orders was significantly influenced by age (83 years) and the pre-arrest morbidity (PAM) index. PAM4 almost always resulted in a DNR order, and PAM score was the only significant contribution to DNR orders under regression analysis. The issuing of DNR orders by geriatric residents was compared with independent assessments by the other two health-care team members. In 50% of cases where significant comorbidity was zero, at least one of the team suggested a reason for a DNR order, with a mean of 1.9 reasons. The most commonly cited reasons were age (24%), depression (20%) and poor prognosis (18%). To evaluate non-patient-related factors involved in DNR decisions, we studied the involvement of patient or family in the decision, and the extent of agreement between health-care team members. Only 3% of patients and 24% of families were involved in the DNR decision. Disagreement with the residents' decisions was 20% for staff nurses and 17% for consultants. Physicians use factors besides comorbidity to make DNR decisions, and further study of such factors is necessary for the development of standardized DNR policies.

In this retrospective study the epidemiology of hip fractures in The Netherlands was evaluated. The number of hip fractures over the period 1972–1987 was collected from the Dutch Centre for Health Care Information (Stichting Informatiecentrum voor de Gezondheidszorg, SIG). The demographic data were collected from the Dutch Centre for Statistics (Centraal bureau voor de Statistiek, CBS). The age-adjusted incidence of hip fractures for both women and men 50 years of age and over, increased linearly over the period 1972–1987. There was also a linear rise in the age-adjusted incidence of hip fractures in women and men 65 years of age and over, but the rise in incidence was equal in both sexes. After the age of 50 years women and men showed an equal proportional increase in the age-specific incidence of hip fractures by 5-year age groups. This proportional increase was independent of the calendar year studied during the period 1972–1987. The increase over time in the age-adjusted incidence of hip fractures in inhabitants 50 years of age and over is the result of changes that act well before the age of 50 years, because the proportional increase in the age-specific incidence of these fractures after the age of 50 years did not change over the period studied. The cohort analysis showed that the age-specific incidence of hip fractures in more recently born birth cohorts is higher than that in birth cohorts born long ago. This observation agrees with the other observations. However the cohort analysis also showed evidence that the increase in the age-specific incidence of hip fractures, with increasing age groups might be smaller in more recently born birth cohorts. Therefore the age-specific incidence of hip fractures in the oldest age group, i.e. in inhabitants 85 years of age and over, might become equal for all birth cohorts. It is concluded that preventive measures and various interventions should be started before the age of 50 years in both women and men.

Bone mineral content was measured by dual photon absorptiometry in 35 women who needed estrogen replacement therapy but did not want the addition of progestogens because they did not want regular bleeding. A total of 23 women were treated with estradiol valerate 1 mg per day over a mean period of 3.7 years; 12 women received conjugated estrogens 0.625 mg per day over a mean period of 5.3 years. The mean values of bone mineral content in both groups did not change. In the women on estradiol valerate, 61% had a decrease, and in those on conjugated estrogens, 67% had a decrease in bone mineral content. However, the calculated decrease per year was within the limits of the intraindividual reproducibility of the measurements. A difference between two measurements with a decrease of > 1.0 g hydroxyapatite/year over a period of > 3 years is larger than the limits of the intraindividual reproducibility. A decrease in bone mineral content > 1.0 g hydroxyapatite/year over a mean period of 3.98 years, SD 0.35, was observed in six of 23 (26%) of the women on estradiol valerate with a mean decrease of 5.28 g hydroxyapatite, SD 0.97. Only one of 12 (8%) of the women on conjugated estrogens had a decrease of 6.1 g hydroxyapatite over a period of 5.2 years. Periodic measurement of bone mineral is recommended in women on estrogen replacement therapy with estradiol valerate 1 mg per day or conjugated estrogens 0.625 mg per day for prevention of postmenopausal bone loss.

The mortality rate and causes of death after a hip fracture were studied in 493 consecutive patients with a hip fracture. All patients were treated in three hospitals in Utrecht, The Netherlands. The mortality rate following hip fractures is high and age dependent. Forty-five patients, 38 women and 7 men, died during the period of hospitalization (9.1%). One year after the date of hip fracture 23.6% of the women had died and 33.0% of the men. Four years after the date of hip fracture the mortality rates in women and men were 44.4% and 55.3%, respectively. Male sex, concomitant illnesses and in-hospital complications are negative determinants of survival. The in-hospital mortality was due to: cerebrovascular accident (n = 7), cardiac decompensation (n = 12), myocardial infarction (n = 4), pulmonary infection (n = 6), intestinal bleeding (n = 1) and sepsis (n = 5). From the registration of death causes we learned that 54 deaths were directly due to the hip fracture, 4 due to bed sores, 34 due to infectious diseases, 62 due to cardiovascular disease, 22 due to cerebrovascular accidents, 14 due to diabetes mellitus, and 33 due to neoplasm. The high mortality rate within the first 8 weeks after the date of hip fracture was mainly attributed to the hip fracture.

The influence of chlorthalidone on bone resorption in immobilized patients treated with mechanical ventilation was studied. Bone resorption was measured by means of urinary excretion of hydroxyproline and calcium. Blood pH was measured because of a possible effect of mechanical ventilation on calcium metabolism. Twenty-five patients were examined, 14 receiving and 11 not receiving chlorthalidone. Patients receiving chlorthalidone over a period of at least five and a maximum of 27 days showed lower hydroxyprolinuria and a higher blood pH value than the non-users. No differences were observed concerning calcium and phosphate metabolism. It is suggested that this slight alkalosis resulting from chlorthalidone may inhibit bone resorption.

The number of hip fractures in women 65 yr of age and over increased from 3416 in 1972 to 8075 in 1987. In men of the same age group the number of hip fractures increased from 1167 in 1972 to 2285 in 1987. This increase can only in part be explained by the increase in the proportion of aged people in the Dutch population. The age-adjusted incidence of hip fractures in The Netherlands rose linearly from 479/100,000 to 669/100,000 per year in women aged 65 yr and over during the period 1972-1987. In men of the same age group the age-adjusted incidence of hip fractures increased linearly from 198/100,000 to 308/100,000 per year over the period studied. The total number of hip fractures in the year 2010 has been estimated at 22,726. The mean duration of a hospital stay because of a hip fracture was 30 days in 1987. The annual need for hospital beds in 1987 for the treatment of hip fractures was calculated at 851. For the year 2010, the annual need for hospital beds, based on a 30-day hospital stay, has been estimated at 1866. Should the duration of a hospital admission due to a hip fracture be reduced to 20 days, then the annual need for hospital beds in 2010 would be 1244.

Addition of human GH (hGH) to primary mouse osteoblasts resulted in rapid and transient induction of the c-fos and c-myc proto-oncogenes and preceded hGH-induced mitogenesis. Human GH-induced c-fos expression was maximal after 30 min, resulting in a 10- to 15-fold increase over unstimulated cells, and returned to prestimulation levels within 60 min of the addition of hGH. Induction of the c-fos gene by hGH was dose dependent and also occurred in the absence of protein synthesis, resulting in superinduction of the c-fos gene. The induction of the c-fos gene by hGH was mediated by a somatotrophic (GH) rather than a lactogenic (prolactin) receptor on primary mouse osteoblasts, as indicated by a 10- to 100-fold greater potency of hGH compared with ovine prolactin in stimulating the expression of the c-fos gene. Primary mouse osteoblasts also induced the c-fos gene in response to epidermal growth factor, insulin-like growth factor-I and several agents, including phorbol 12-myristate 13-acetate (TPA), forskolin and A23187, that are known to activate signal transduction pathways involved in the action of growth factors. Addition of hGH to primary mouse osteoblasts did not result in increased phosphoinositide breakdown, while selective deactivation of the diacylglycerol—protein kinase C and inositol 1,4,5—trisphosphate—Ca2+ pathways by long-term TPA pretreatment or depleting intracellular Ca2+ stores had no effect on hGH-induced c-fos expression. Human GH did not alter basal cyclic AMP levels in mouse osteoblasts. The immediate consequences of GH—receptor interaction as well as the mechanism of signal transduction leading to induction of the c-fos gene remain, therefore, unresolved.

The aim of the study was to investigate the usefulness of urinary fluoride excretion in evaluating fluoride therapy. In a prospective study, 35 patients with osteoporosis were treated for about 44 months with a mean dosage of 31.4 mg fluoride ion per day. Urinary fluoride excretion and serum alkaline phosphatase activity were measured at 3-month intervals. Bone mineral content (BMC) was measured in L2-L4 with dual-photon absorptiometer. The mean number of BMC measurements was 5.7 per patient. The interindividual reproducibility for measurements in 10 patients was 2.1%. For each individual, the regression coefficient of BMC for the period of treatment was calculated. Responders were defined as those who had a positive value and nonresponders had 0 or a negative value. The percentage responders was 83%. Between responders and nonresponders no differences were found for age, fluoride dosage, duration of treatment, or changes in serum alkaline phosphatase activity. Urinary fluoride excretion was higher in responders than in nonresponders (p less than 0.001) and a positive correlation (p less than 0.001) was obtained between the changes in BMC and urinary fluoride excretion. In the responders, 90% had a urinary fluoride excretion greater than 8 mg/24 h. All nonresponders had a urinary fluoride excretion less than 8 mg/24 h. Urinary fluoride excretion is a valuable predictor of BMC response during fluoride therapy for osteoporosis.

The mortality rate and causes of death after a hip fracture were studied in 493 consecutive patients with a hip fracture. All patients were treated in three hospitals in Utrecht, The Netherlands. The mortality rate following hip fractures is high and age dependent. Forty-five patients, 38 women and 7 men, died during the period of hospitalization (9.1%). One year after the date of hip fracture 23.6% of the women had died and 33.0% of the men. Four years after the date of hip fracture the mortality rates in women and men were 44.4% and 55.3%, respectively. Male sex, concomitant illnesses and in-hospital complications are negative determinants of survival. The in-hospital mortality was due to: cerebrovascular accident (n = 7), cardiac decompensation (n = 12), myocardial infarction (n = 4), pulmonary infection (n = 6), intestinal bleeding (n = 1) and sepsis (n = 5). From the registration of death causes we learned that 54 deaths were directly due to the hip fracture, 4 due to bed sores, 34 due to infectious diseases, 62 due to cardiovascular disease, 22 due to cerebrovascular accidents, 14 due to diabetes mellitus, and 33 due to neoplasm. The high mortality rate within the first 8 weeks after the date of hip fracture was mainly attributed to the hip fracture.

A group of 60 healthy early postmenopausal women participating in an ongoing study on the effect of habitual calcium intake on the rate of cortical bone loss at the radius, were subjected to additional skeletal measurements at the lumbar spine and femoral neck. The women were between 58 and 64 years of age, and 3 to 10 years postmenopausal. No correlations were found between habitual calcium intake (range 560 to 2580 mg/day) and either bone mineral content of the radius, the lumbar spine and the femoral neck, or spine deformity index. Body mass index was found to be positively correlated with bone mass indices of the radius (decrease of BMD and BMD) and femoral neck (BMC), but not with of the lumbar spine (BMC, BMD and SDI), even after adjustments had been made for confounding factors. Although the rate of cortical bone loss at the radius correlated significantly with bone mineral content of lumbar spine and femoral neck, the error in predicting bone mass of the lumbar spine or the femoral neck from longitudinal measurements of cortical bone at the radius was high. The rate of cortical bone loss did not correlate with the spine deformity index. We conclude that in healthy women in early menopause, the bone mineral content of both the appendicular and the axial skeleton are not influenced by habitual calcium intake. A higher body mass index has a protective effect on the appendicular skeleton but appears to be less protective to the axial skeleton. Longitudinal measurements of cortical bone mass are of limited value to predict bone density of the appendicular and axial skeleton.

Bone metabolism was studied in 17 acromegalic patients, who responded to either medical treatment with bromocriptine (12 patients), or to transsphenoidal surgery (5 patients). Parameters of bone turnover decreased, e.g. serum acid phosphatase (9.2 ± 0.7 vs 8.1 ± 0.6 U/l, P < 0.05) and the ratio of hydroxyproline/creatinine (33.6 ± 4.4 vs 18.3 ± 2.0, P < 0.01) in the urine. No changes were observed in parathyroid function or concentrations of calcitonin. Serum 1,25-dihydroxycholecalciferol decreased (32.6 ± 3.6 vs 20.6 ± 1.8 ng/1, P < 0.01) and 24,25-dihydroxycholecalciferol increased (4.3 ± 0.6 vs 6.7 ± 1.0 μg/l, P < 0.05). No correlation between the percentual changes in serum growth hormone levels and 1,25-dihydroxycholecalciferol was found, suggesting an indirect effect of growth hormone on the renal 25-hydroxycholecalciferol-1-alpha-hydroxylase. The possible mechanisms involved are discussed, including the effects of growth hormone and somatomedin on bone.

The mechanism of thyroid action on bone was studied in 15 patients with thyrotoxicosis and 14 patients with hypothyroidism. The patients were studied twice: when they were thyrotoxic or hypothyroid and when they had returned to a euthyroid state. Parameters of bone turnover showed a decrease when hyperthyroid patients became euthyroid: serum calcium (2.51 ± 0.04 vs 2.38 ± 0.03 mmol/l, P< 0.05), acid phosphatase (11.7 ± 0.7 vs 8.3 ± 0.4 U/l, P < 0.01), alkaline phosphatase (124 ± 11 vs 98 ± 8 U/l, P P P < 0.01). These parameters showed an increase when hypothyroid patients became euthyroid: serum calcium (2.36 ± 0.03 vs 2.48 ± 0.04 mmol/l, P < 0.01), alkaline phosphatase (60 ± 4 vs 84 ± 8 U/l, P < 0.05) and the hydroxyproline/creatinine ratio in the urine (15.9 ± 4.3 vs 25.3 ± 3.2, P < 0.05). Changes in the calcium regulating hormones, parathyroid hormone, calcitonin and vitamin d metabolites, were not observed when hyperthyroid patients became euthyroid. When hypothyroid patients were treated a decrease in serum levels of 1.25-dihydroxyvitamin d (32.6 ± 4.6 vs 17.9 ± 2.5 ng/l, P P < 0.01). The possible mechanisms of thyroid action on bone are discussed. The presented findings are in accordance with a direct effect of thyroid hormones on bone in thyrotoxicosis. An additional factor could be somatomedin, that might also be involved in changes in bone turnover in hyper- and hypothyroidism.

In an incubation experiment the Human Serum Albumin (HSA) binding of 99 m Tc-MDP (electrolytically labeled) and 99 m Tc(Sn)-MDP is established. During the incubation some pertechnetate is formed and in the case of 99 m Tc(Sn)-MDP also some hydrolyzed 99 m Tc. The HSA binding of 99 m Tc-MDP is less than the HSA binding of 99 m Tc(Sn)-MDP as established with gel chromatography, TCA-precipitation, ammonium sulfate precipitation and ultrafiltration. TCA-precipitation seems to be an insufficient method for determining the protein binding of 99 m Tc(Sn)-MDP. The urinary excretion in rats shows only one 99 m Tc-compound in both cases. The bone seeking properties of the urine-excreted 99 m Tc-compound were confirmed in another rat.

Attempts were made to demonstrate the presence of specific oestrogen binding proteins ("receptors") in bone cells. High speed cytosol preparations of bone were incubated with several concentrations of radioactive oestradiol alone and with radioactive oestradiol in the presence of a specific antioestrogen, Nafoxidine. Separation of bound and free oestradiol was carried out by dextran coated charcoal treatment and by sucrose gradient ultracentrifugation. Several types of bones likely to be oestrogen-sensitive were investigated: human femoral heads, human phalanx, rat and rabbit calvaria, humeri and femora of female rats. In all experiments we were unable to demonstrate the presence of specific oestrogen receptors in bone cell cytosol indicating that the direct effect of oestrogens on bone, if present, is not mediated by specific oestrogen receptors.

GH action on cartilage is thought to be mainly mediated through the somatomedins produced by the liver. However, recent studies using cultured chondrocytes also point to a direct mitogenic action of GH. Besides, a direct action of GH on fetal rat tibiae has been demonstrated. This study is the first to show stimulation of thymidine uptake as well as DNA synthesis under the influence of physiological concentrations of human and chicken GH in fetal chicken osteoblasts in culture.

In 30 patients with renal insufficiency, a biopsy specimen was taken from the iliac crest and processed to obtain non-decalcified sections for morphometric evaluation. The bone volume was normal. There was an increased amount of osteoid tissue, increased bone resorption and an abnormal amount of fibrous tissue. With the aid of correlation calculations and factor analysis, four factors were extracted which expressed the influence of parathyroid hormone on bone tissue, the degree of mineralization and the relation between bone volume and bone surface, the relation between bone tissue and measured space, and non-active bone resorption.

More evidence has recently been obtained indicating that growth hormone (GH) has a direct effect on bone. However, it is not clear which cell type reacts to the hormone. The present study used osteoblast-like cells derived from sequentially digested fetal mouse calvaria. Separately cultured tractions resulted in populations enriched in cells with a more or a less differentiated phenotype. The results showed that GH acts on the cells released last, i.e. those with more characteristics of the osteoblast. In these cells, GH induced strong mitogenic activity. Prolactin was not active.

15 Staphylococcus aureus strains were isolated from 15 patients with staphylococcal bacteremia. Eight of these strains were shown to be tolerant for cloxacillin. Cloxacillin-tolerant strains were also tolerant for most of the cephalosporins tested except for cephapirin. Strains were not tolerant for clindamycin and gentamicin. Penicillin-tolerant staphylococci showed a high degree of synergism between gentamicin and cloxacillin or cephalothin and gentamicin.