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Evaluation of surgical training in Denmark is competency based with no requirement for a specific number of procedures. This may affect monitoring of surgical progress adversely and cause an underestimation of the time needed to acquire surgical competencies. We investigated the number of common surgical procedures performed by trainees. Trainees’ and consultants’ expectations from the training program were also investigated.

To investigate the possible use of oral phosphate as an activator of bone remodeling in coherence treatment of osteoporosis, 82 postmenopausal females, aged 50–75 years, were randomized to treatment with oral phosphate (750, 1500, or 2550 mg/day) or placebo for 7 days and followed for 4 months thereafter. All patients had sustained at least one previous fracture of the distal forearm and had a bone mineral content of the contralateral forearm or bone mineral density of the lumbar spine lower than normal mean for age. Urinary phosphate/creatinine ratio increased in a dose-dependent fashion during treatment (P<0.001), whereas no significant changes were seen in serum phosphate or serum calcium. Serum parathyroid hormone (PTH) rose significantly (P<0.05) during treatment to a maximum of 36 and 33% in the groups receiving 1500 and 2250 mg/day, respectively, whereas serum 1,25-dihydroxycholecalciferol remained unchanged. In the group receiving 1500 mg/day, mean serum osteocalcin was increased in the period from day 1 to day 28 (P<0.05), but no significant changes were observed in urinary hydroxyproline/creatinine ratio, or serum bone alkaline phosphatase. We conclude that a short course of oral phosphate treatment increases serum PTH considerably. Furthermore, 1500 mg/day but not 2250 mg/day increases serum osteocalcin. No clear biochemical evidence, however, of increased activation of bone remodeling could be demonstrated in either group.

Type I collagen makes up more than 90% of bone matrix. Therefore, analysis of antigens related to collagen formation and degradation in bone should provide good and specific estimates of both bone resorption and bone formation rates. In this study we measured serum levels of the pyridinoline cross‐linked telopeptide domain of type I collagen (ICTP) as a marker of bone resorption and serum carboxy‐terminal propeptide of type I procollagen (PICP) as a marker of bone formation. Serum levels of the two antigens were correlated to histomorphometric indices of bone resorption and bone formation calculated from iliac crest bone biopsies in a group of 18 individuals with high‐ and low‐turnover bone disease (myxedema, primary hyperparathyroidism, and thyrotoxicosis). After logarithmic transformation the regression of S‐ICTP on volume‐referent resorption rate (BRs/R/BV) was significant (r= 0.61, p< 0.01, SEM/Y = 56%). S‐ICTP also showed a significant regression on the volume‐referent cancellous bone balance (r= −0.45, p< 0.05, SEM/Y = 412%).S‐PICP was significantly correlated to the mineral appositional rate (r= 0.53, p< 0.05) and volume‐referent bone formation rate (r= 0.61, p< 0.01, SEM/Y = 48%). The correlation to bone turnover as expressed in the activation frequency was also highly significant (r= 0.61, p< 0.01, SEM/Y = 51%). No significant correlation with wall thickness or bone balance was demonstrable per remodeling cycle. Thus, assays employing antigens that reflect collagen formation and degradation are useful instruments for the evaluation of rates of bone remodeling in metabolic bone disease.

A single dose of 2.5 mg prednisone leads to a significant transient decrease in serum osteocalcin, which is only demonstrated by frequent serum sampling. The aim of the present study was to evaluate whether a single dose of inhaled beclomethasone dipropionate causes transient changes in serum osteocalcin, indicating a systemic effect on bone cells. In a double-blind, placebo controlled, cross-over design we evaluated the effects of single doses of 250 μg and 1000 μg beclomethasone on the circadian rhythm in serum osteocalcin. Fifteen normal subjects aged 2 3-38 years were studied twice with an interval of one week with hourly blood sampling from 16.30 until 1 7.00 the following day; 1000 μg beclomethasone, but not 250 μg, suppressed serum cortisol by 14.4±6.7% (p=0.03). Neither of the beclomethasone doses significantly altered the time pattern of serum osteocalcin. We conclude that a single inhaled dose of beclomethasone in the therapeutical range does not acutely influence osteoblastic activity as judged from serial measurements of serum osteocalcin.

Bone remodeling constitutes the life-long renewal process of bone whereby the mechanical integrity of the skeleton is preserved. It implies the continuous removal of bone (bone resorption) followed by synthesis of new bone matrix and subsequent mineralization (bone formation). Moreover, bone remodeling is an integral part of the calcium homeostatic system together with the kidneys and the gut. The ever ongoing removal of old bone by osteoclastic resorption and subsequent coupled osteoblastic formation of new bone leads to liberation of calcium and matrix constituents into the serum. The matrix constituents liberated into the blood during bone resorption can be used as markers of bone resorption in serum or urine and components liberated during osteoblastic matrix synthesis are putative markers of bone formation.Extensive research over the last 10 years has characterized a wide variety of new markers of cellular activity in bone (Table 1). Serum and urine levels of these

Aim:This study was undertaken to examine the effects of long-term vitamin D treatment on calcium, phosphate and magnesium homeostasis at organ level in hypoparathyroid patients.Methods:Fifteen vitamin D-treated hypoparathyroid patients were studied, eight of the patients in a combined 47Ca kinetic and calcium, phosphate and magnesium balance study. Results were compared with a matched control group of 12 normal individuals.Results:All the patients had normal serum levels of calcium, phosphate and magnesium. Absolute intestinal calcium absorption was increased (P<00001). Urinary calcium excretion was normal, but active tubular calcium reabsorption (TmCa/glomerular filtration rate) was low (P<0·001). Bone resorption rates and bone mineralization rates were very low (P<0001 and P<0·05). Twenty-four-hour urinary hydroxyproline excretion and serum cross-linked carboxyterminal telopeptide of type I were in the upper normal range. Serum alkaline phosphatase was normal, but serum carboxyterminal propeptide of human type I procollagen and serum osteocalcin were significantly reduced (P<0·05). Calcium balance was positive and significantly different from controls (P<0·001). All parameters from phosphate homeostasis were normal. Intestinal magnesium absorption was low though not significantly different from normal (P= 0·06). Urinary excretion of magnesium was not significantly higher than normal, but renal magnesium reabsorption was reduced (P<0·001). Magnesium balance was low, though the difference was not significant (P<0·06).Conclusion:Long-term vitamin D treatment in hypoparathyroid patients resulted in a positive calcium balance. Bone turnover was very low. Results of bone markers and resorption rate were conflicting. Vitamin D treatment apparently normalized the abnormalities previously found in phosphate homeostasis of hypoparathyroid patients. Magnesium homeostasis was disturbed, with a more negative balance compared with normal subjects, implying a state of magnesium deficiency in these patients.European Journal of Endocrinology13652–60

Langdahl BL, Loft AGR, Eriksen EF, Mosekilde L, Charles P. Bone mass, bone turnover and body composition in former hypothyroid patients receiving replacement therapy. Eur J Endocrinol 1996;134:702–9. ISSN 0804–4643The aim of the present cross-sectional study was to disclose whether long-term thyroxine replacement therapy (TRT) in primary hypothyroidism causes osteopenia. We compared 36 adult biochemically and clinically euthyroid patients who had received TRT for more than 5 years (mean 13 years) for primary hypothyroidism with 80 sex- and age-matched normal controls. Height, body weight and lean body mass were similar, but the patients had 21% higher fat body mass (p < 0.01) than their controls. Furthermore, compared to controls the patients had 29% higher serum thyroxine (T4) and 31% higher serum free T4index (FT4I) levels (p < 0.001), whereas serum triiodothyronine (T3) and FT3I levels were both reduced by 7% (p < 0.05). In the patients, serum TSH was reduced significantly (p < 0.001). No significant differences were observed between patients and normals in regional or total bone mineral content or bone mineral density levels, apart from 20% higher lumbar bone mineral content among the premenopausal patients (p < 0.05). Surprisingly, the mean serum calcium level was slightly elevated (2.38 ± 0.08 vs 2.33 ± 0.07 nmol/l, p < 0.001), serum phosphate decreased (1.13 ± 0.19 vs 1.23 ± 0.16 mmol/l, p < 0.01) and 24-h renal calcium excretion was reduced by 19% (p < 0.05). No changes were observed in serum magnesium, intact parathyroid hormone or calcitriol. The biochemical markers of bone resorption (serum carboxyterminal telopeptide of type I collagen, renal excretion of hydroxyproline, pyridinoline and deoxypyridinoline) and formation (serum levels of carboxyterminal propeptide of type I procollagen, osteocalcin and total and bone alkaline phosphatase) were similar in the two groups. We conclude that long-term thyroxine replacement therapy in primary hypothyroidism does not exert a negative effect on bone mass or alter bone turnover.Bente L Langdahl, University Department of Endocrinology and Metabolism, Aarhus Amtssygehus, Tage Hansensgade 2, DK-8000, Aarhus C, Denmark

Summary: The acute effect of 25 and 50 g of alcohol on the variation in serum osteocalcin, a specific and sensitive marker of bone formation, and on serum cortisol and serum parathyroid hormone (PTH)(1–84) was calculated in 6 normal young adults. They were studied during three periods, each lasting from 4 p.m.–7:30 a.m. Alcohol was ingested between 4:15 and 5 p.m. during period two and three. Blood was taken at 4 p.m. and every 15 minutes from 4:30 til 6 p.m., followed by hourly sampling until 12 p.m. The last blood sample was taken after an overnight fast at 7:30 a.m. Initial and end values before and after alcohol ingestion did not differ significantly from control values. Repeated measures analysis of variance showed that 50 g of ethanol decreased serum osteocalcin significantly (P<0.02) and increased serum cortisol (P<0.05) during the 4–12 p.m. interval. The interaction of 50 g of ethanol on the variation in serum osteocalcin was already significant during the first 2 hours (P<0.02), where no significant effect on serum cortisol could be detected. Although insignificant, the same pattern was observed after 25 g of alcohol. There was no significant change in the variation of serum iPTH(1–84) during the 4–6 p.m. after alcohol intake. We conclude that 3–4 drinks of alcohol taken over 45 minutes decreases serum osteocalcin in a dose-dependent way. The time lag between changes in serum osteocalcin and cortisol indicates that the decrease in serum osteocalcin is not related to the increase in serum cortisol.

Summary: Serum levels of total alkaline phosphatase activity (S-T-AP), wheat germ lectin-precipitated alkaline phosphatase activity (S-L-AP), and bone Gla-protein immunoreactivity (S-BGP) were measured in 26 patients (23 females and 3 males) aged 35–73 years (mean 59 years) with primary hyperparathyroidism (n=7), hyperthyroidism (n=9), and hypothyroidism (n=10) in whom the bone mineralization rate (m) was determined by47Ca-kinetics (continuously expanding calcium pool model). A weak positive correlation (r=0.42,P<0.05) was found between S-T-AP and m, which in the range from 0–18 mmol Ca/day could be estimated with a standard error of 4.6 mmol/day. A closer correlation (r=0.65,P<0.001) was found between S-L-AP and m which was estimated with an error of 3.9 mmol Ca/day. The AP activity in the supernatant showed no significant correlation to m (r=0.11,P>0.50). The highest correlation coefficient (r=0.81,P<0.001) was found between S-BGP and m which could be predicted with an error of 3.4 mmol Ca/day. S-BGP showed a closer correlation to S-L-AP (r=0.71,P<0.001) than to S-T-AP (r=0.58,P<0.01). We concluded that S-L-AP predicts bone mineralization at organ level better than S-T-AP in selected metabolic bone disorders and that the supernatant activity shows no relation to bone turnover. We find the assay easy to handle and suitable for large-scale use in the diagnosis and monitoring of metabolic bone disease.

The effects of human calcitonin on bone mineral content and certain biochemical markers of bone metabolism were evaluated in a 2-12-month treatment period in seven patients with osteogenesia imperfecta. S-calcium, S-alkaline phosphatase, S-immuno-reactive parathyroid hormone and the urinary excretion of calcium were found to be within the normal range before and during the treatment period. After 4-5 months of therapy, a slight increase in the urinary excretion of hydroxyproline was observed, but the values were still within the normal range. The bone mineral content, measured in the forearm, remained unchanged during the treatment period. Side effects were common, in two cases resulting in discontinuation of the treatment. We concluded that, with the dose of human calcitonin used, it was impossible to detect any beneficial effect in patients with osteogenesis imperfecta.

Hyperthyroidism is characterized by increased bone turnover and resorptive activity. Similar changes in remodeling are seen in osteoporosis. To study the pathogenetic role of thyroid hormone in osteoporosis, we measured concentrations of free and total thyroid hormones and investigated the sensitivity of the skeleton toward thyroid hormones in 14 osteoporotic, 16 estrogen‐treated, and 15 normal postmenopausal women with comparable thyroid status. Triiodothyronine (T3, 60 μg/day for 7 days) was administered to the three groups. The skeletal response was assessed by monitoring bone alkaline phosphatase (BAP), osteocalcin (BGP), and pyridinium cross‐linked telopeptide domain of type I collagen (ICTP) in serum and urinary excretion of hydroxyproline (OHP), pyridinoline (PYR), and deoxypyridinoline (DPR) at days 0, 8, 15, and 57. Women on estrogen replacement therapy exhibited lower bone turnover than the normal postmenopausal women. Markers of bone formation were reduced by 19–43% and markers of resorption by 22–48%. The osteoporotic women displayed lower bone mass at the lumbar spine and the distal forearm (p< 0.01–0.001), but the levels of biochemical markers of bone formation and resorption were comparable to values obtained in the normal postmenopausal women. T3stimulation caused significant increases (pvalues ranging between 0.05–0.001) in all three groups of the resorptive markers: ICTP (47%, 47%, 45%), OHP (29%, 30%, 33%), PYR (43%, 27%, 51%), and DPR (42%, 24%, 59%). Of the formative markers, only BGP increased significantly (32%, 40%, 47%) (p< 0.001). At day 57, however, all three formative markers increased compared with day 15 (p< 0.05–0.001). No significant differences in bone markers were demonstrated between groups. In the osteoporotic group, as the only group, serum calcium increased (p< 0.05) and serum PTH fell (p< 0.05). In conclusion, osteoporosis and estrogen substitution are not characterized by altered concentrations of thyroid hormones or responsiveness to thyroid hormones at the level of individual bone cells; however, altered responses pertaining to PTH and calcium were detected.

Thyroid hormones exert major influences on bone and mineral metabolism. Hyperthyroidism induces an accelerated bone loss and may thereby increase the risk of low-energy fractures. Hypothyroidism has the opposite effect. This review describes the effect of thyroid hormones on bone and mineral metabolism at the cellular, tissue, and organ level. Clinical aspects of disturbed thyroid function on bone metabolism also are discussed.

Hyperthyroidism is characterized by increased bone turnover and resorptive activity. Similar changes in remodeling are seen in osteoporosis. To study the pathogenetic role of thyroid hormone in osteoporosis, we measured concentrations of free and total thyroid hormones and investigated the sensitivity of the skeleton toward thyroid hormones in 14 osteoporotic, 16 estrogen‐treated, and 15 normal postmenopausal women with comparable thyroid status. Triiodothyronine (T3, 60 μg/day for 7 days) was administered to the three groups. The skeletal response was assessed by monitoring bone alkaline phosphatase (BAP), osteocalcin (BGP), and pyridinium cross‐linked telopeptide domain of type I collagen (ICTP) in serum and urinary excretion of hydroxyproline (OHP), pyridinoline (PYR), and deoxypyridinoline (DPR) at days 0, 8, 15, and 57. Women on estrogen replacement therapy exhibited lower bone turnover than the normal postmenopausal women. Markers of bone formation were reduced by 19–43% and markers of resorption by 22–48%. The osteoporotic women displayed lower bone mass at the lumbar spine and the distal forearm (p< 0.01–0.001), but the levels of biochemical markers of bone formation and resorption were comparable to values obtained in the normal postmenopausal women. T3stimulation caused significant increases (pvalues ranging between 0.05–0.001) in all three groups of the resorptive markers: ICTP (47%, 47%, 45%), OHP (29%, 30%, 33%), PYR (43%, 27%, 51%), and DPR (42%, 24%, 59%). Of the formative markers, only BGP increased significantly (32%, 40%, 47%) (p< 0.001). At day 57, however, all three formative markers increased compared with day 15 (p< 0.05–0.001). No significant differences in bone markers were demonstrated between groups. In the osteoporotic group, as the only group, serum calcium increased (p< 0.05) and serum PTH fell (p< 0.05). In conclusion, osteoporosis and estrogen substitution are not characterized by altered concentrations of thyroid hormones or responsiveness to thyroid hormones at the level of individual bone cells; however, altered responses pertaining to PTH and calcium were detected.

Summary: Bone mineral content (BMC), bone mineral density, and metacarpal dimensions were studied in 50 women with Turner's syndrome aged 21–45 years in relation to karyotype, estrogen treatment, physical fitness, and biochemical markers of bone turnover. No differences were found between the 25 women with karyotype 45,X and women with other karyotypes. Forty-six women had received estrogen. Significant partial correlations were found between bone mineral density of the forearm and duration of estrogen treatment and physical fitness. BMC of the lumbar spine corrected for vertebral height (BMC(C)spine) was directly correlated with duration of estrogen treatment and height, marginally correlated with physical fitness, and inversely correlated with age. Outer metacarpal width was positively correlated with duration of estrogen treatment, age at initiation of therapy, and body weight. The diameter of medullary space showed negative correlation with physical fitness and height, and positive correlation with age at initiation of estrogen treatment. Cortical thickness was positively correlated with duration of estrogen treatment, physical fitness, and height. No convincing effects of estrogen could be demonstrated in women below the age of 30. Above the age of 30, all bone mineral measurements were markedly elevated in women treated for longer than the average of this age group. BMC(C)spine was inversely correlated with biochemical markers of bone formation. Our results demonstrate that estrogen treatment and physical fitness are important determinants of bone mineral status in Turner's syndrome and add to the evidence that estrogen treatment increases BMC in Turner's syndrome.

The diagnosis of pulmonary embolism (PE) remains one of the most difficult in clinical medicine, and the diagnostic value of lung scintigraphy has been questioned. To evaluate the observer variation in the interpretation of ventilation-perfusion lung scanning in the diagnosis of PE, 87 lung scintigrams from consecutive patients with phlebography-proven deep venous thrombosis and without clinical signs of PE were randomly mixed with 50 reference lung scintigrams from patients with PE symptoms. The scintigrams were reevaluated blind by two experienced clinical physiologists. Each observer evaluated each lung scintigram twice and recorded whether the lung scan was normal or abnormal. If it was abnormal, the location and number of segment defects were registered. The intraobserver agreement, including number and location of segments, ranged from 0.77 to 0.85 and for the diagnosis of PE from 0.88 to 0.92 with a kappa of 0.80 – 0.84. The values for the interobserver agreement for the diagnosis of PE were 0.73 – 0.80 with a kappa of 0.56 – 0.67. It is concluded that in the interpretation of ventilation-perfusion lung scintigraphy the use of a simple scheme — deciding whether there is segmental ventilation-perfusion mismatch or not — has a good reproducibility with a high kappa for inter- and intraobserver variation and can serve as a simple routine method for diagnosing PE.

With the aim of investigating whether patients with otosclerosis suffer from a generalized bone disorder, a histomorphometric analysis of trabecular bone from the iliac crest was performed. Iliac crest biopsies from 10 patients with otosclerosis and 20 normal controls were obtained after tetracycline double labelling and examined by histomorphometry. No significant differences were found in the estimates of density and remodelling of bone between patients and sex and age-matched normal controls. Qualitatively the bone specimens showed no signs of any generalized bone disorder.

Estrogen stimulates osteoblastic collagen production in vitro, but whether the same stimulation takes place in vivo is still unknown. To test the stimulatory effects of a combined estrogen‐gestagen regimen in vivo we monitored serum levels of the carboxy‐terminal propeptide of human type I procollagen (S‐PICP) in a group of 12 osteoporotic women over a 150 week treatment period. Spinal bone mineral content (BMC) increased to a maximum of 5% over pretreatment values around week 90. Serum alkaline phosphatase (S‐AP) and serum bone gla protein (S‐BGP) both fell from initial values of 220 U/liter and 39 ng/ml, respectively, to 146 U/liter (p< 0.01) and 27.2 ng/ml (NS) around week 60 and remained reduced over the remaining treatment period. S‐PICP also fell from 117 to 68 μg/liter at week 60 and 70 μg/ml at week 150 (P< 0.01). This is equal to a reduction to 32 ± 10% pretreatment levels. The reduction in S‐PICP was not significantly different from that of the other two markers of bone formation (S‐AP and S‐BGP). Thus, provided the metabolic clearance of PICP remains unaltered after hormone replacement therapy, no major stimulation of osteoblastic collagen type I synthesis was demonstrable during estrogen‐gestagen treatment in this population of osteoporotic women. The changes in bone markers seen in this study are therefore consistent with an estrogen‐mediated reduction in the frequency of remodeling activation. Because of the reduction in bone turnover and methodologic limitations of bone marker assays, however, smaller increases in the amount of bone formed per activation could remain undetectable.

Eighty-five patients, age 48 to 77 y with postmenopausal crush fracture osteoporosis, were investigated using a 7-d combined calcium balance and 47Ca tracer-kinetic turnover method taking the dermal calcium loss into account. Individual dietary records were obtained based on a 4-d registration at home before hospital admission and on questioning by a dietitian. The following dietary constituents were estimated: energy content, protein, methionine, cysteine, calcium, phosphate, magnesium, coffee, fiber and vitamin C. All patients were served individual diets based on the dietary records during study. Dietary calcium was measured in duplicates of all the meals served. All urine and feces were collected and analyzed for calcium content. The 47Ca kinetic data were analyzed according to a modification of the expanding calcium pool model. The overall calcium balance correlated significantly to energy content (r= 0.31, P< 0.005), protein (r= 0.22, P< 0.05), calcium (r= 0.28, P< 0.01), phosphate (r= 0.27, P< 0.02) and coffee (r= -0.21, P< 0.05). However, a multiple backward linear regression analysis disclosed that only calcium (rp= 0.38, P< 0.0005) and coffee intake (rp= -0.25, P< 0.05) significantly influenced calcium balance. The equation was: calcium balance (mmol/d) = 0.14 × (dietary calcium, mmol/d) - 0.0016 × (coffee intake, mL/d) - 3.62. A coffee intake in excess of 1000 mL could induce an extra calcium loss of 1.6 mmol calcium/d, whereas intakes of 1–2 cups of coffee per day would have little impact on calcium balance.

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