Dermal Calcium Loss Research Articles

Calcium Intake and Metabolism in Infants and Young Children: A Systematic Review of Balance Studies for Supporting the Development of Calcium Requirements

ABSTRACTDetermining calcium requirements for infants and children is vital due to high calcium needs for growth. Balance studies enable comprehensive measurement of calcium metabolism and can support nutrient requirement development. This systematic review summarizes evidence from mass balance and isotopic studies in children aged 0–4 y to address key questions on calcium loss and absorption/retention identified by an expert group developing calcium requirements. Literature searches were implemented in multiple electronic databases to June 2020. Balance studies assessing calcium intake, loss, absorption, or retention in healthy children were eligible. A newly developed risk-of-bias assessment tool was used for balance studies, and a modified Grades of Recommendation, Assessment, Development, and Evaluation approach determined strength of evidence. Altogether, 23 studies (15 mass balance; 8 isotope) with 485 total participants were included. Only 3 studies were of children >6 mo. Mass balance studies suggested infant feed components may influence calcium balance. The random-effects model meta-regression on 42 mass balance study arms showed an average net calcium retention of 40.4% among infants aged 0–6 mo (β = 0.404 [95% CI: 0.302, 0.506]). Isotope studies suggested calcium intake of 240 to 400 mg/d may promote optimal calcium absorption with minimal loss, and intake from human milk may lead to greater absorption and retention efficacy than formula or solid foods. Most studies had low risk of bias. Strength of evidence was low due to variability in infant feedings, limited endogenous and dermal calcium loss measures, and few studies isolating calcium effects. To improve certainty of the body of evidence, more balance studies isolating effects of calcium intake in this age group are needed. Future work on calcium needs should incorporate both balance measures and biological endpoints of importance (e.g. bone mineral density or content) to determine adequate calcium intake for growth in infants and children.

Commentaries on Viewpoint: Fragile bones of elite cyclists: to treat or not to treat?

Commentaries on Viewpoint: Fragile bones of elite cyclists: to treat or not to treat?

Calcium loss in sweat does not stimulate PTH release: A study of Bikram hot yoga

It has been hypothesized that sweat loss during exercise causes a disruption in calcium homeostasis that activates bone resorption and over time leads to low bone mineral density. The purpose of this small pilot study was to determine whether dermal calcium loss from a bout of excessive sweating during light intensity physical activity triggers an increase in biomarkers of bone resorption. Biochemical markers related to bone homeostasis were measured before and after a 90 min Bikram hot yoga practice performed in a room heated to 105 °F with 40 % humidity. Participants were five females with a mean age of 47.4 ± 4.7 years. Nude body weight, serum total calcium (Ca2+), free ionized calcium, albumin, parathyroid hormone (PTH) and CTX-I were measured before and after a Bikram hot yoga practice. Mean estimated sweat loss was 1.54 ± 0.65 L, which elicited a 1.9 ± 0.9 % decrease in participant’s body weight. Mean Ca2+ concentration in sweat was 2.9 ± 1.7 mg/dl and the estimated mean total calcium lost was 41.3 ± 16.4 mg. Serum ionized Ca2+ increased from 4.76 ± 0.29 mg/dl to 5.35 ± 0.36 mg/dl after the Bikram hot yoga practice (p = 0.0118). Serum PTH decreased from pre- 33.9 ± 3.3 pg/ml to post- 29.9 ± 2.1 pg/ml yoga practice (p = 0.0015) when adjusted for hemoconcentration (PTHADJ), implying a decrease in PTH secretion. We conclude that calcium loss in sweat during 90 min of Bikram hot yoga did not trigger an increase in PTH secretion and did not initiate bone resorption.

Dermal Calcium Loss Is Not the Primary Determinant of Parathyroid Hormone Secretion during Exercise.

Exercise can cause a decrease in serum ionized calcium (iCa) concentration, which stimulates parathyroid hormone (PTH) secretion and activates bone resorption. We postulated that dermal Ca loss during cycling exercise is the major determinant of the serum iCa, PTH, and bone resorption (C-terminal telopeptide of type 1 collagen [CTX]) responses. To investigate this, women (n = 13) and men (n = 12) age 18 to 45 yr performed the same exercise bout under cool (18°C) and warm (26°C) conditions. Exercise was 60 min of cycling at ~75% of peak aerobic power. Sweat samples were obtained during exercise using a skin patch method, and blood samples were obtained before and during exercise and during 60 min of recovery. Sweat volume and estimated sweat Ca loss were 50% higher for the warm condition than the cool condition. Despite this, there were no differences between thermal conditions in the changes (mean, 95% confidence interval [95% CI]) in iCa (cool, -0.07 mg·dL; 95% CI, -0.16 to 0.03); warm, -0.07 mg·dL; 95% CI, -0.20 to 0.05), PTH (cool, 34.4 pg·mL; 95% CI, 23.6-45.2; warm: 35.8 pg·mL; 95% CI, 22.4-49.1), or CTX (cool, 0.11 ng·mL; 95% CI, 0.08-0.13; warm, 0.15 ng·mL; 95% CI, 0.11-0.18). Adjusting for exercise-related shifts in plasma volume revealed a marked decline in vascular iCa content in the first 15 min of exercise (cool, -0.85 mg·dL; 95% CI, -1.01 to -0.68; warm, -0.85 mg·dL; 95% CI, -1.05 to -0.66), before substantial sweat Ca loss had occurred. This indicates that dermal Ca loss was not the primary trigger for the increases in PTH and CTX during exercise. Further research is necessary to understand the causes and consequences of the disruption in Ca homeostasis during exercise and specifically the extravascular shift in iCa.

Calcium, PTH, And CTX Responses to Treadmill Walking During Different Thermal Environments in Older Adults

Serum ionized calcium (iCa) decreases and parathyroid hormone (PTH) and c-terminal telopeptides of type I collagen (CTX; marker of bone resorption) increase during endurance exercise in younger and older adults. Evidence from equine models suggests this may be due to dermal calcium loss. PURPOSE: To determine if exercise in a warm environment exaggerates the decrease in iCa and increases in PTH and CTX compared to a cool environment. METHODS: Women (n=5) and men (n=7) aged 61-78 years performed two identical 1-hour treadmill walking bouts under warm (~28°C) and cool (~21°C) conditions at ~75% of maximal heart rate. iCa, PTH, and CTX were measured every 15 minutes starting 15 minutes before and continuing for 60 minutes after exercise. Sweat calcium loss was estimated from sweat volume and sweat calcium concentration. Changes in iCa, PTH, and CTX were adjusted for plasma volume shifts. Between and within group differences were evaluated using maximum likelihood estimation in a repeated measures model. RESULTS: There was no difference in sweat calcium loss between thermal conditions. iCa decreased similarly during exercise in both conditions (W: -0.16, 95% CI: -0.28, -0.08 mg/dL; C: -0.16, 95% CI: -0.24, -0.04 mg/dL). After adjusting for plasma volume shifts, change in iCaADJ was significant only for the warm condition (-0.24, 95% CI: -0.44, -0.04 mg/dL), but there was no difference between conditions. PTH increased similarly during exercise in both conditions (W: 16.4, 95% CI: 6.2, 26.5 pg/mL; C: 17.3, 95% CI: 8.1, 26.4 pg/mL). Adjusting for plasma volume shifts did not change the results. CTX increased similarly in both conditions (W: 0.08, 95% CI: 0.05, 0.11 ng/mL; C: 0.08, 95% CI: 0.01, 0.16 ng/mL), and adjusting for plasma volume shifts did not change the results. There were no differences between conditions for any outcome, even after adjusting for plasma volume shifts. CONCLUSION: Differing thermal conditions do not appear to be a major factor in the decrease in iCa and the increases in PTH and CTX observed during exercise in older adults. This may be due to the low sweat calcium loss during both conditions or small temperature difference. Future studies should determine if there are sex- or age-related differences that modify the relationship between sweat calcium loss and the activation of bone resorption during exercise.

Bone Mineral Density and Regular Swimming: Observational and Interventional Studies

Although exercise in general is beneficial for enhancing bone mineral density (BMD), people who participate in non‐weight bearing, low impact, activities are at a greater risk for bone loss. A recent study indicates that excessive dermal calcium loss through sweat will create bone demineralization and decrease bone mineral density in some athletes. Swimming exercise is characterized by low impact activity but sweat loss is much smaller than other endurance‐trained athletes. First, using the cross‐sectional study, BMD was measured using dual‐energy x‐ray absorptiometry in 44 sedentary controls (56±1 years), 48 runners (54±1 years), and 27 swimmers (57±1 years). Body mass and body fatness were significantly lower in runners than in swimmers and sedentary controls. Total (whole‐body) BMD was not different among the groups. Runners had significantly higher leg BMD than swimmers and sedentary controls (1.38±0.02 vs. 1.33±0.04 and 1.32±0.02 g/m2). There were no differences in other regional (head, arms, trunk, ribs, pelvis and spine) BMD between the three groups. We then determined changes in BMD after 3 months of swimming exercise intervention in 24 previously sedentary adults (58±2 years). Total and regional BMD did not change. Collectively, our observational and interventional findings indicate that swimming exercise is not associated with a greater bone mineral density.

Acute Calcium Ingestion Attenuates Exercise-Induced Disruption of Calcium Homeostasis

Exercise is associated with a decrease in bone mineral density under certain conditions. One potential mechanism is increased bone resorption due to an exercise-induced increase in parathyroid hormone (PTH), possibly triggered by dermal calcium loss. The purpose of this investigation was to determine whether calcium supplementation either before or during exercise attenuates exercise-induced increases in PTH and C-terminal telopeptide of Type I collagen (CTX; a marker of bone resorption). Male endurance athletes (n = 20) completed three 35-km cycling time trials under differing calcium supplementation conditions: 1) 1000 mg of calcium 20 min before exercise and placebo during, 2) placebo before and 250 mg of calcium every 15 min during exercise (1000 mg total), or 3) placebo before and during exercise. Calcium was delivered in a 1000-mg·L(-1) solution. Supplementation was double-blinded, and trials were performed in random order. PTH, CTX, bone-specific alkaline phosphatase (BAP; a marker of bone formation), and ionized calcium (iCa) were measured before and immediately after exercise. CTX increased and iCa decreased similarly in response to exercise under all test conditions. When compared with placebo, calcium supplementation before exercise attenuated the increase in PTH (mean ± SE: 55.8 ± 15.0 vs 74.0 ± 14.2 pg·mL(-1), P = 0.04); there was a similar trend (58.0 ± 17.4, P = 0.07) for calcium supplementation during exercise. There were no effects of calcium on changes in CTX, BAP, and iCa. Calcium supplementation before exercise attenuated the disruption of PTH. Further research is needed to determine the effects of repeated increases in PTH and CTX on bone (i.e., exercise training) and whether calcium supplementation can diminish any exercise-induced demineralization.

Bone Density in Competitive Cyclists

To investigate current theories of the contributing factors to osteopenia/osteoporosis in competitive cyclists, we present a narrative review of published cross-sectional studies investigating plausible etiologies of decreased bone density in competitive cyclists. Aggregate from multiple published studies as cited. Bone mineral density in cyclists appears to be correlated positively to the cumulative amount of bone loading forces experienced over a lifetime. However, decreases in bone mineral density are noted over the short term if bone loading forces are removed, despite previous gains. There also appears to be a negative correlation between bone mineral density and dermal calcium losses during exercise. Data are mixed on whether calcium supplementation improves bone mineral density in this setting. No correlation was found between sex hormones and bone mineral density in the competitive cyclists studied. Knowledge of the underlying contributors to reduced bone mineral density in cyclists can aid in making preventative and therapeutic recommendations that potentially could decrease the morbidity and mortality related to osteoporosis.

Acute Effects Of Intense Exercise And Calcium Supplementation On Calcium Homeostasis And Bone Markers

Although exercise is accepted as having favorable effects on bone, under certain conditions exercise has been associated with a decrease in bone mineral density (BMD). One potential mechanism is an exercise-induced increase in parathyroid hormone (PTH), a potent stimulator of bone resorption, possibly triggered by dermal calcium loss. PURPOSE: To determine whether calcium (Ca) supplementation before or during exercise attenuates exercise-induced increases in PTH and C-terminal telopeptide of type I collagen (CTX, a marker of bone resorption), when compared with placebo. METHODS: Twenty competitive male athletes (cyclists and triathletes) completed three 35-km time trials on a cycle ergometer under differing Ca supplementation conditions: 1) 1000 mg of Ca 20 min before exercise and placebo during, 2) placebo before and 250 mg of Ca every 15 min during exercise (1000 mg total), or 3) placebo before and during the exercise bout. Supplementation was double-blinded and rides were performed in random order. PTH, CTX, ionized calcium (iCa), and bone-specific alkaline phosphatase (BAP) were measured before and immediately after exercise. RESULTS: PTH and CTX increased and iCa decreased significantly in response to exercise under all test conditions. Ca before exercise significantly attenuated the increase in PTH relative to placebo; there was a similar trend for Ca during exercise. There were no significant effects of Ca on changes in CTX, BAP, and iCa.TableCONCLUSION: Ca supplementation before, and perhaps during, exercise attenuated disruptions of Ca homeostasis. Further research is needed to determine the effects of increases in PTH and CTX on bone and whether Ca supplementation can diminish any exercise-induced demineralization.

BMD Decreases Over the Course of a Year in Competitive Male Cyclists

Male cyclists have been found to have low BMD in cross-sectional studies. Changes in BMD values over 1 yr of training and competition were studied in 14 male cyclists. BMD decreased significantly at the total hip, neck, trochanter, and shaft regions but not the lumbar spine. This first prospective study of cyclists showed a decrease in BMD over the course of 1 yr. Cross-sectional studies have shown that some endurance athletes, and cyclists in particular, have low BMD. Whether vigorous cycle training is causally related with low BMD remains unknown. Changes in BMD values over 1 yr of training and competition were studied in 14 male road cyclists, 27-44 yr of age. Subjects were randomized to receive 1500 (500 mg with meals) or 250 mg of supplemental calcium citrate daily. BMD measurements were obtained at pre-, mid-, post-, and off-season time points over 1 yr. Dermal calcium loss during exercise was estimated using a patch collection technique to examine calcium loss as a potential mediator of changes in BMD. Using paired t-tests, BMD was found to decrease significantly from pre- to off-season at the total hip, neck, shaft, and trochanter regions (relative changes of -1.5 +/- 2.1%, -0.7 +/- 2.1%, -0.9 +/- 2.1%, and -1.0 +/- 1.2%, respectively, all p < 0.05). The 1.0 +/- 1.2% decrease in BMD at the lumbar spine failed to reach statistical significance (p = 0.079). There were no differences in changes in BMD between the calcium supplementation groups. The 2-h dermal calcium loss was estimated at 136.5 +/- 60.5 mg. Higher dermal calcium losses were associated with lower baseline BMD values at the total hip, neck, and shaft (all p < 0.05), but were not significantly associated with changes in BMD. This study suggests that high intensity cycle training may adversely affect BMD. Excessive dermal calcium loss during exercise may be a contributing factor, but mechanisms remain to be elucidated.

Exercise and Calcium Supplementation

Exercise-induced sweat calcium losses have been reported as substantial in male athletes. The first aim of the study was to quantify the increase in 24-h total dermal calcium losses and the net changes in calcium retention in active sportswomen after a 1-h strenuous exercise session. A second aim was to determine the effectiveness of calcium supplementation to offset any calcium loss. Twenty-six premenopausal sportswomen completed three 8-d intervention phases in a randomized-order, crossover design. The three phases were placebo+no exercise (control), placebo+exercise, and 400 mg of calcium as calcium carbonate (TUMS Ultra) twice daily+exercise. The supervised exercise was 1 h.d(-1) cycling at 65-70% of heart rate reserve. A controlled diet of approximately 450 mg.d(-1) of calcium and 24-h pooled urine and fecal collections allowed determination of calcium balance on days 5-8 of each phase. Twenty-four-hour dermal collections were made at the end of each phase using a whole-body washdown procedure. Exercise increased (P<0.05) dermal calcium losses (means+/-SD, 92+/-49 vs 79+/-31 mg.d(-1) in the nonexercise intervention period), which was no longer significant (P=0.14) when calcium supplementation was provided (83+/-49 mg.d(-1)). Higher (P<0.01) urinary calcium excretion during calcium supplementation is suggestive of higher net calcium absorption. Exercise did not affect urinary calcium excretion indicating lack of compensation for dermal losses. Net calcium retention was positive only during the exercise+calcium supplementation intervention period. Calcium supplementation can correct for negative calcium balance attributable to low calcium dietary intake and additional dermal losses from exercise.

Acute Effects of 2 Hours of Moderate-Intensity Cycling on Serum Parathyroid Hormone and Calcium

Previous studies have found that serum parathyroid hormone (PTH) increases in response to relatively short (<60 minutes), intense bouts of exercise, possibly as a result of decreases in serum calcium. Whether longer, less intense exercise also stimulates an increase in PTH is not known. The effects of 2 hours of moderate-intensity cycling on serum PTH and calcium were investigated in 20 competitive male cyclists, aged 22-45 years. Serum concentrations of PTH and calcium were measured before and after exercise. Dermal calcium loss was estimated using patch collections and loss of sweat. There were increases in PTH from 40.6 +/- 15.6 to 69.5 +/- 25.5 pg/mL (P < 0.001) and in serum calcium from 9.3 +/- 0.3 to 9.6 +/- 0.5 mg/dL (mean +/- standard deviation, P = 0.001) in response to exercise. Contraction of plasma volume explained the rise in calcium but not PTH. Dermal calcium loss was estimated at 138.0 +/- 71.9 mg for the 2-hour exercise bout. Neither the change in serum calcium nor the dermal calcium loss was significantly related to the increase in PTH. The study demonstrated that prolonged exercise stimulates PTH secretion. The effects of such transient increases in PTH on bone metabolism are not known.

Bone Density - Triathlete

HISTROTY: A male triathlete aged 43 years underwent bone mineral density (BMD) screening after learning that some endurance athletes have low BMD. He was healthy with no fracture history or family history of bone disease. He was taking no prescription medications and denied using any performance-enhancing substances. He had been competing in triathlons for 16 years. BMD was assessed using dual-energy x-ray absorptiometry (DXA). He had low BMD at both the lumbar spine (L1 -4, L-spine) and total hip. After 6 months of his routine off-season weight training and continued endurance activity his BMD improved 9.5% at the L-spine and 2.5% at the hip. Following 6 months of continued endurance training and little weight training, his BMD decreased by 8.2% at the L-spine and 1% at the hip. For the first 6 months, his mean hours of training by modality were as follows: weight lifting 10.1+/− 3.3, cycling 19.0+/− 7.8, running 7.1+/− 3.8, swimming 5.0+/− 1.5. For the second 6 month period, his hours by modality were as follows: weight lifting 1.9+/− 2.4, cycling 16.7+/− 4.2, running 12.9+/− 2.7, swimming 5.0+/− 1.5. EXAMINATION: Examination revealed a well-nourished, well-developed fit male. Vital signs were normal. He had no boney deformities. Scleras were normal color with no bluish tint. He had no stigmata of thyroid dysfunction, malabsorption, hypogonadism or cortisol excess. DIFFERENTIAL DIAGNOSIS: Disturbed calcium homeostasis due to dermal calcium loss Disregulation of bone remodeling due to excess cortisol production Disregulation of bone remodeling due to hypogonadism TESTS AND RESULTS: L-spine BMD was 0.861, 0.943 and 0.871 g/cm2 at baseline, month 6 and month 12 respectively. Total hip BMD was 0.857, 0.879 and 0.870 g/cm2 at baseline, month 6 and month 12. Bone mass was 2.054, 2.140 and 2.051 kg at baseline, month 6 and month 12. Body weight varied from 57.76 to 58.95 and 57.82 kg at baseline, month 6 and month 12. WORKING DIAGNOSIS: Endurance exercise-induced loss of BMD. TREATMENT AND OUTCOMES: Recommend year-round weight training Consider limiting endurance activity, particularly weight supported activities such as swimming and cycling Consider increasing calcium and vitamin D intake through dietary modification or supplementation

Changes in Bone Mineral Content in Male Athletes

To determine changes in bone mineral content (BMC) in male athletes, to examine the mechanisms of changes, and to evaluate the effects of intervention. Dual-energy x-ray absorptiometry (DEXA) tests were administered over a 2-year period, and calcium loss during training was determined by analysis of sweat and urine. Calcium supplementation was administered during year 2. SETTING--A midsouth university. Eleven members of a college Division I-A basketball team. Based on observed calcium loss, athletes received differential levels of calcium supplementation. Intervention commenced the week prior to the fall training season and continued through postseason play. MAIN OUTCOME MEASURE--Changes in BMC. Total body BMC decreased 3.8% from preseason to midseason of year 1 (mean decrease, 133.4 g, P = .02), increased nonsignificantly by 1.1% (mean increase, 35.3 g, P = .22) during the offseason, but decreased an additional 3.3% during summer months when practices resumed (mean decrease, 113.1 g, P = .01). Dermal calcium loss averaged 247 mg [corrected] per training session. From preseason to late summer, there was an overall decrease of 6.1% in total BMC and a 10.5% decrease in BMC of the legs. Calcium supplementation was associated with significant increases in BMC and lean body mass. Bone loss is calcium related and exercise is positively related to BMC provided that calcium intake is sufficient to offset dermal loss.

Calcium Metabolism in Postmenopausal Osteoporotic Women is Determined by Dietary Calcium and Coffee Intake ,

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.

Calcium metabolism in postmenopausal osteoporosis: The influence of dietary calcium and net absorbed calcium

A group of 85 females aged 48-77 years with postmenopausal crush fracture osteoporosis were investigated using a 7 day combined calcium balance and calcium tracer kinetic turnover study to assess the influence of dietary calcium and net absorbed calcium on bone metabolism. During the study, patients were on their habitual diet, as determined by a prestudy registration. Dietary calcium was measured after double serving of all the meals. All urine and feces were collected and analyzed for calcium content. Bone mineralization rate and bone resorption rate were determined by applying the continuously expanding calcium pool model to the tracer kinetic data. Urine calcium excretion and net absorbed calcium were correlated (r = 0.64, p less than 0.0001) with the following equation: urinary excreted calcium (mmol/day) = 2.4 + 0.4 X net absorbed calcium (mmol/day). Dermal calcium loss was not correlated with net absorbed calcium or urinary calcium. The net amount of absorbed calcium necessary to balance urinary and dermal losses was calculated to be 4.2 mmol calcium per day. The daily calcium intake necessary for obtaining a net absorbed calcium in excess of the urinary and dermal calcium losses and thereby ensure skeletal integrity was estimated to be 34.2 mmol calcium per day compared to an average intake of 27.9 +/- 7.6 (mean +/- SD) mmol/day. Net absorbed calcium correlated negatively to bone resorption rate (r = -0.31, p less than 0.005) and positively to bone mineralization rate (r = 0.29, p less than 0.01) and to calcium balance (r = 0.66, p less than 0.0001). Dietary calcium intake and calcium balance correlated positively (r = 0.38, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Primary hyperparathyroidism: evaluated by 47calcium kinetics, calcium balance and serum bone-Gla-protein.

Combined 47Calcium kinetic and calcium balance studies with correction for dermal calcium loss were performed in thirteen patients with primary hyperparathyroidism (PHP), in whom serum bone-Gla-protein (S-BGP) was measured, and in ten matched controls. Dietary calcium was normal in PHP but both net (7.9 +/- 1.4 mmol Ca day-1 in PHP v. 3.5 +/- 0.9 mmol Ca day-1 in normals (mean +/- SE] and true (11.1 +/- 1.6 v. 6.8 +/- 0.9 mmol Ca day-1) intestinal absorbed calcium were enhanced (P less than 0.05). The renal calcium excretion (10.9 +/- 0.8 v. 5.1 +/- 0.4 mmol Ca day-1, P less than 0.001) and the dermal calcium loss (2.5 +/- 0.3 v. 1.5 +/- 0.1 mmol Ca day-1, P less than 0.02) were increased in PHP. Both patients and controls were in a negative calcium balance (P less than 0.01 and P less than 0.001, respectively) without any difference between the groups (P greater than 0.10). Mineralization (12.0 +/- 1.7 v. 4.8 +/- 0.8 mmol Ca day-1, P less than 0.02) and resorption rates (17.6 +/- 2.5 v. 7.9 +/- 0.6 mmol Ca day-1, P less than 0.02) were increased in PHP and S-BGP correlated positively to both variables (r = 0.64, P less than 0.05 and r = 0.62, P less than 0.05, respectively). Serum immunoreactive parathyroid hormone correlated positively to serum calcium (r = 0.69, P less than 0.01) but not to the calcium kinetic data.

Calcium metabolism evaluated by 47calcium-kinetics: a physiological model with correction for faecal lag time and estimation of dermal calcium loss.

Sixty-two calcium balance and 47Ca-turnover studies were performed in 51 individuals to evaluate the accuracy and the sensitivity of the methods. The data were analysed according to a modification of the expanding calcium pool model using an improved Bauer-Carlsson-Lindquist (BCL) formulation and an iterative computer procedure. A 7-day whole body retention curve (R1) combined with a retention curve constructed from excretion data alone (R2) was used to estimate dermal calcium loss (d) and to demonstrate the significance of individual corrections for delay in faecal excretion (faecal lag time = delta t). The mean d was 1.58 mmol Ca/day. The introduction of delta t improved the goodness of fit of the data to the model. delta t based on 47Ca-kinetics was superior to a fixed delta t of zero (P less than 0.01) or 2 days (P less than 0.05). The model derived renal calcium excretion rate was highly correlated (r = 0.98, P less than 0.001) to the chemical measured excretion rate. A similar highly significant correlation [RS = 0.78 (Spearman), P less than 0.001] was found between the model derived delta t and the carmine red delta t. These results indicate a high accuracy of the model. The directly measured parameters showed an excellent reproducibility with a coefficient of variation (CV) less than 4%. The reproducibility of the derived parameters was acceptable (CV = 10-20%) except for the balance (CV = 72%).

Calcium metabolism evaluated by 47Ca kinetics: estimation of dermal calcium loss.

Seventy-seven calcium balance and 47Ca turnover studies were performed in normal volunteers (n = 15) and in patients with osteoporosis (n = 12), primary hyperparathyroidism (n = 8), osteogenesis imperfecta (n = 5), medullary carcinoma of the thyroid (n = 4), thyrotoxicosis (n = 2) and intestinal bypass for obesity (n = 11). After intravenous injection of 20 microCi of 47Ca two retention curves of 47Ca were obtained: R1(t) directly measured on a whole-body counter and R2(t) calculated from the cumulated daily excretions of 47Ca in urine and faeces. The data were fitted to a modification of the continuously expanding exchangeable calcium pool model. Dermal calcium loss was estimated from the serum 47Ca specific radioactivity curve and the constantly increasing difference between the two retention curves. The median dermal calcium loss in 77 studies was 1.50 mmol 24 h-1 1.73 m-2 (range 0.13-4.60). The dermal calcium loss might be overestimated by redistribution of tracer or by eventual insufficient collection of urine and faeces. The possible influences of these errors have been evaluated. Patients with primary hyperparathyroidism had a greater (P less than 0.02) dermal calcium loss (2.64 mmol; range 0.80-4.50) than a control group (1.38 mmol; range 1.25-2.34).

Studies in calcium metabolism. II. Effects of low calcium and variable protein intake on human calcium metabolism

Six healthy males consumed diets containing about 0.1 g calcium/day at three levels of protein intake: 0.9, 12, and 24 g nitrogen/day. Daily urinary calcium excretion on the 0.9 nitrogen diet was 51 mg, 99 mg on the 12 g nitrogen diet, and 161 mg on the 24 g nitrogen diet. A calcium supplement of 0.9 g for four subjects on the 12 g nitrogen diet caused an increase in urinary calcium from 68 to 160 mg/day. Varying the calcium and protein intake had no effect on dermal calcium loss or serum calcium. Five subjects had the least negative calcium balance on the 12 g nitrogen diet. Increase in urinary calcium is not likely to result solely from enhancement of intestinal calcium absorption. Our data suggest that increased glomerular filtration with possible inhibition of renal tubular reabsorption of calcium may be an additional mechanism responsible for the calciuretic effect during high-protein intake.