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Biomedical subjects

M Peacock

Publications and source records attributed to M Peacock.

At least 19 recordsLinked to original sources

Calcium supplementation and increases in bone mineral density in children.

BACKGROUND: Increased dietary intake of calcium during childhood, usually as calcium in milk, is associated with increased bone mass in adulthood; the increase in mass is important in modifying the later risk of fracture. Whether the increase is due to the calcium content of milk, however, is not certain. METHODS: We conducted a three-year, double-blind, placebo-controlled trial of the effect of calcium supplementation (1000 mg of calcium citrate malate per day) on bone mineral density in 70 pairs of identical twins (mean [+/- SD] age, 10 +/- 2 years; range, 6 to 14). In each pair, one twin served as a control for the other; 45 pairs completed the study. Bone mineral density was measured by photon absorptiometry at two sites in the radius (at base line, six months, and one, two, and three years) and at three sites in the hip and in the spine (at base line and three years). RESULTS: The mean daily calcium intake of the twins given placebo was 908 mg, and that of the twins given calcium supplements was 1612 mg (894 mg from the diet and 718 mg from the supplement). Among the 22 twin pairs who were prepubertal throughout the study, the twins given supplements had significantly greater increases in bone mineral density at both radial sites (mean difference in the increase in bone mineral density: midshaft radius, 5.1 percent [95 percent confidence interval, 1.5 to 8.7 percent]; distal radius, 3.8 percent [95 percent confidence interval, 1.4 to 6.2 percent]) and in the lumbar spine (increase, 2.8 percent [95 percent confidence interval, 1.1 to 4.5 percent]) after three years; the differences in the increases at two of three femoral sites approached significance (Ward's triangle in the femoral neck, 2.9 percent; greater trochanter, 3.5 percent). Among the 23 pairs who went through puberty or were postpubertal, the twins given supplements received no benefit. CONCLUSIONS: In prepubertal children whose average dietary intake of calcium approximated the recommended dietary allowance, calcium supplementation increased the rate of increase in bone mineral density. If the gain persists, peak bone density should be increased and the risk of fracture reduced.

Absorptiometry, Photon

Interpretation of bone mass determinations as they relate to fracture: implications for asymptomatic primary hyperparathyroidism.

Determination of bone mass is currently the most clinically useful measurement of bone strength and of fracture risk. Interpretation of bone mass determination as it relates to fracture has been developed largely from studies of age-related bone loss. A decrease in bone mass and an increase in fracture incidence with aging are universal phenomena that are causally related by virtue of the major contribution bone mass makes to skeletal strength. Over 70% of the skeleton's strength to resist fracture resides in its mineral content in vitro. Clinically, the relationship between trauma and fracture is complex, and in the general population, fracture appears as a random event occurring more frequently as bone mass decreases. In the individual, measurement of bone mass in relation to the range of bone mass and the fracture incidence of the reference population provides an estimate of the risk of sustaining a fracture in the future. In primary hyperparathyroidism, interpretation of a bone mass determination must take into account the effect of the disease activity on the skeleton against the background of universal age-related changes in bone mass and fracture incidence. This general relationship is likely to be altered by at least three unique effects that parathyroid hormone may have on the skeleton: (1) parathyroid hormone has a differential effect on cortical and cancellous bone; (2) it has a biphasic effect on bone that is concentration dependent; and (3) it alters bone quality and architecture.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon

Calcium absorption efficiency and calcium requirements in children and adolescents.

Optimizing bone mass of young adults is important in the prevention of osteoporosis in later life. To achieve maximal peak bone mass, dietary calcium and its absorption need to be sufficient for skeletal growth and consolidation and for obligatory losses in urine, feces, and sweat. Direct measurements of skeletal accretion, obligatory losses, and of dietary calcium and absorption in children and adolescents have either not been done or are incomplete. From the measurements available and from extrapolated data in adults, it appears likely that many children and adolescents are not absorbing sufficient calcium in relation to their intake to achieve maximal bone mass.

Absorption

The architecture of cancellous and cortical bone in femoral neck fracture.

The architecture of cancellous bone as well as quantity and quality is considered important in maintaining mechanical integrity. To determine whether abnormalities of architecture occur in femoral neck fracture we measured trabecular width and number in iliac crest bone biopsies of 68 women with femoral fracture and compared them with data from a postmortem series of age-matched women without known bone disease. Cortical thickness was measured in 27 of the fracture patients and 17 controls. After exclusion of ten biopsies with increased osteoid surface no significant difference was seen in mean trabecular width or number between fracture patients and subjects without fracture. Both thinning of trabeculae and loss of trabeculae contributed to low bone volume in femoral fracture patients. Direct measurements of trabecular number correlated with calculated mean trabecular plate density (P less than 0.001), and the percentage of trabeculae at any one of a range of trabecular widths in the fracture biopsies was similar to that in non-fracture subjects. No difference was seen in the architecture of cancellous bone with age, fracture trauma or between subcapital and intertrochanteric fracture in fracture subjects. Cortical thickness, however, was related to age in both fracture and control subjects (P less than 0.05). There was no difference in cortical thickness between age-matched fracture and control subjects. Patients with intertrochanteric fracture had lower cortical thickness (P less than 0.02) and were older (P less than 0.01) than patients with subcapital fracture.

Aged

Osteomalacia and osteoporosis in femoral neck fracture.

Iliac crest bone histomorphometry, plasma and urine biochemistry and clinical history were examined in 78 unselected patients (68 women, 10 men) at the time of femoral fracture. Histological abnormalities occurred in 56 of the 78 biopsies. The commonest of these was a low bone volume of less than 15% which, irrespective of other abnormal histological features, was present in 37 of the biopsies. On the basis of the histomorphometry, patients could be classified into four main groups. Normal histomorphometry (bone volume greater than 15%, osteoid surfaces less than 24%, mineralising surface greater than 60%) was present in 22 patients, 23 had osteoporosis as the only abnormality (bone volume less than 15%, osteoid surface less than 24%, mineralising surface greater than 60%), nine had osteomalacia (osteoid surfaces greater than 24%, mineralising surface less than 60%, osteoid width greater than 13 microns) and 13 had decreased mineralising surfaces. Of the remainder, five had increased osteoid surface and six had insufficient osteoid to assess mineralising surface. Plasma and urine biochemistry in the four groups showed that, compared to age-matched controls, all groups had reduced plasma albumin. In comparison to the group with normal histomorphometry, patients with osteoporosis had a higher plasma calcium (P less than 0.01), tubular reabsorption of calcium (P less than 0.05) and plasma vitamin D binding protein (P less than 0.01); patients with osteomalacia had a higher plasma creatinine (P less than 0.02) and parathyroid hormone (P less than 0.02) and lower plasma 24,25-dihydroxyvitamin D (P less than 0.02), urinary calcium/creatinine ratio (P less than 0.02) and tubular reabsorption of phosphate (P less than 0.02). The biochemistry in patients with decreased mineralising surface was no different from patients with a normal biopsy. The prevalence of both osteoporosis and osteomalacia increased with age and, in subjects over the age of 90, osteoporosis occurred in 71% of patients and osteomalacia occurred in 29% of patients. The osteomalacic group were significantly older than the other three groups (P less than 0.05). The histomorphometry did not relate to the site of fracture (subcapital or intertrochanteric). A history of stroke, gastrectomy, rheumatoid arthritis, steroid treatment, thyroid disease, alcohol abuse and anti-convulsant therapy was present in patients with femoral fracture but did not relate to any particular histomorphometric classification.

Age Factors

Calcium absorption in children estimated from single and double stable calcium isotope techniques.

In order to determine whether the specific activity in a single serum sample estimates calcium absorption, six healthy children participated in a study using stable isotopic calcium tracers, one given orally and the second intravenously. High-resolution, fast atom bombardment mass spectrometry was used to quantify the 44Ca and 42Ca tracers in serum and urine. Subjects ingested 250 mg of calcium (215 mg calcium enriched with 35 mg 44Ca) in the form of a chewable calcium citrate malate tablet with a standard meal, followed 30 min later with an i.v. injection of 42Ca tracer. Blood for tracer determinations was obtained at 90, 120, 150, 180, and 300 min after oral ingestion, and a urine sample was obtained 24 h after oral calcium tracer administration. The average calcium absorption estimated from the ratio of urinary tracers was 41.4 +/- 8.2%. This study indicates that the level of oral tracer in serum taken 150 min post-ingestion is significantly correlated (r = 0.85, p less than 0.05) with calcium absorption, as determined by the tracer levels in the urine. These results show that an oral stable isotopic tracer coupled with a single blood sample can be used to estimate calcium absorption in children.

Absorption

Spinal osteoporosis in men.

In 94 men with crush fracture, 40 were found to have primary osteoporosis. Cross-sectional measurements of a number of variables related to bone in these 40 patients were compared to the values in various groups of healthy men aged 20-96. In healthy men, metacarpal and femoral cortical area/total area, bone volume, osteoid surfaces, seam and trabecular width, plasma dihydroepiandrosterone and estrone, and radiocalcium absorption fell with age, whereas eroded surfaces, trabecular number, urine hydroxyproline and calcium/creatinine ratios, plasma alkaline phosphatase, estradiol, androstenedione, cortisol and testosterone remained constant with age. As compared with healthy men, men with primary osteoporosis had reduced femoral cortical area/total area (P less than 0.05), and Singh grade (P less than 0.001) and in seven there was a history of forearm or femoral fracture. On iliac crest biopsy, bone volume (P less than 0.001) and trabecular number (P less than 0.01) were decreased. Plasma alkaline phosphatase (P less than 0.02) was increased but urine hydroxyproline and calcium excretion were not significantly raised. Calcium balance was negative due to failure of absorption to match urinary calcium loss and radiocalcium absorption (P less than 0.01) and plasma 1,25-dihydroxyvitamin D (P less than 0.05) were reduced.

Adult

Comparison of the effects of oral and transdermal oestradiol administration on oestrogen metabolism, protein synthesis, gonadotrophin release, bone turnover and climacteric symptoms in postmenopausal women.

We compared the effect of administering oestradiol via the transdermal or oral routes in six and eight postmenopausal women respectively. Although both treatments achieved similar plasma levels of oestradiol, oral administration led to much greater increases in plasma levels of oestrone and the sulphates and glucuronides of oestradiol, oestrone and oestriol than transdermal treatment (P less than 0.001). Both treatments reduced plasma FSH; from 42 +/- 10 (SE) IU/l to 30 +/- 2 IU/l with oral and from 46 +/- 7 IU/l to 28 +/- 6 IU/l with transdermal treatment. Urine calcium excretion fell from 0.41 +/- 0.06 (molar ratio to creatinine) to 0.17 +/- 0.02 with oral and from 0.25 +/- 0.06 to 0.13 +/- 0.02 with transdermal treatment. Patients' symptoms were improved by both treatments. These changes were related to the plasma oestradiol concentration but not to that of oestrone. Oral, but not transdermal, treatment stimulated hepatic protein synthesis as shown by increased plasma levels of both vitamin-D-binding globulin and sex-hormone-binding globulin. We conclude that although both oral and transdermal oestradiol reduce postmenopausal bone loss, gonadotrophin secretion and symptoms, oral treatment also leads to hepatic stimulation and extensive metabolism of oestradiol, both of which may increase side-effects without conferring additional benefit.

Administration, Oral

Contrasting microanatomy of idiopathic and corticosteroid-induced osteoporosis.

Previous studies of microanatomic changes in normal bone with age have suggested that underlying differences in bone remodeling between male subjects and female subjects give rise to different patterns of bone loss. The relationship between microanatomic and histologic levels of organization are herein examined in two groups of osteoporotic subjects, one with idiopathic and the other with corticosteroid-induced osteoporosis. Using tissue from the iliac crest, total trabecular surface and trabecular width and number were measured, together with bone volume and static and dynamic indices of formation (osteoid surface, seam width, mean wall thickness, lamellar thickness, calcification fronts, and mineralization rate) and resorption (total resorption cavities and osteoclast incidence). The results suggest that while a similar loss of trabecular bone volume is common to both groups, there is a marked distinction in the distribution of the remaining bony tissue and indices of remodeling. A decline in trabecular number accompanied by a relative increase in resorption characterized both sexes with primary osteoporosis, whereas a decline in trabecular width associated with depressed formation was the predominant feature in the secondary disease. Thus trabecular attenuation is principally the manifestation of depressed formation, while trabecular discontinuity is primarily the manifestation of bone resorption.

Adrenal Cortex Hormones

Distributions of neuropeptides in the human esophagus.

The distributions of nerve cells and fibers with immunoreactivity for the peptides substance P, somatostatin, enkephalin, vasoactive intestinal peptide, gastrin-releasing peptide, and neuropeptide Y and the enzyme tyrosine hydroxylase were examined in 25 samples of human esophagus. These were compared with samples of stomach and intestine. In the smooth muscle of the muscularis externa, the muscularis mucosae, and beneath the epithelium, the most abundant nerve fibers contained vasoactive intestinal peptide and neuropeptide Y, in contrast to the scarcity of substance P, enkephalin, somatostatin, and gastrin-releasing peptide. Gastric and intestinal samples contained dense populations of fibers containing vasoactive intestinal peptide, neuropeptide Y, substance P, and enkephalin in the equivalent layers, but somatostatin- and gastrin-releasing peptide-immunoreactive fibers were scarce. Complete coexistence of vasoactive intestinal peptide and neuropeptide Y in nerve fibers within the muscle layers was demonstrated in the esophagus, but not in gastric and intestinal samples. The myenteric plexus along the length of the esophagus contained cell bodies and fibers reactive for vasoactive intestinal peptide, neuropeptide Y, enkephalin, and substance P. Somatostatin-immunoreactive cell bodies were very rare in the myenteric plexus, no gastrin-releasing peptide-immunoreactive cell bodies were seen, and both somatostatin and gastrin-releasing peptide-immunoreactive fibers were rare. In the upper esophagus, striated muscle bundles did not contain nerve fibers reactive for these peptides but immunoreactive fibers were seen in the muscularis mucosae and subepithelium. It is concluded that the esophagus has a different pattern of innervation by peptide-containing neurons than the stomach and intestines. Esophageal neurons can be classified into separate classes on the basis of their peptide content.

Adult

Local action of oral 1,25-dihydroxycholecalciferol on calcium absorption in osteoporosis.

To investigate whether low calcium absorption in osteoporosis improves by increasing 1,25-dihydroxyvitamin D both systemically in plasma and locally in gut, the effects of oral 25-hydroxycholecalciferol and oral 1,25-dihydroxycholecalciferol on plasma 1,25-dihydroxy-vitamin D (1,25-(OH)2D) and calcium absorption were studied in 20 postmenopausal patients with vertebral osteoporosis. In 10 patients taking oral 0.25 micrograms 1,25-dihydroxycholecalciferol twice daily for 7 d, calcium absorption increased more than in 10 patients taking oral 40 micrograms 25-hydroxycholecalciferol once daily for 7 d (p less than 0.02) despite both groups having a similar increase in plasma 1,25-(OH)2D. These results support the view that the major effects of oral 1,25-dihydroxycholecalciferol on absorption is due to a local action on the gut and that it is possible to increase calcium absorption in osteoporosis with oral 1,25-dihydroxycholecalciferol without increasing its undesirable action on bone resorption.

Administration, Oral

Effect of chronic administration of ammonium sulfate on phosphatic stone recurrence.

Urine alkalinization favours the formation of calcium phosphate (CaP) and struvite stones. In this retrospective study we analyze the effect of chronic urinary acidification on phosphatic stone recurrence. Twenty-four patients with CaP-struvite recurrent stones and persistently high urinary pH were divided in two groups: group A, 11 patients who failed to lower the urinary pH below 5.5 during a standard acid load test: group B, 13 patients with preserved acidification power. Ammonium sulfate 2-3 g/day was given for 4.7 and 6.5 years to groups A and B, respectively. A persistent reduction in urinary pH, relative saturation for CaP and stone formation rate was observed in both groups. The treatment did not cause systemic acidosis as long as renal function remained normal. Urinary daily excretion of Ca and P as well as their renal tubular handling did not change with time. Results suggest acidifying agents might be useful in preventing recurrence of CaP-struvite stones even in the presence of a mild acidification defect and encourage undertaking properly controlled prospective trials.

Adult

Vitamin D metabolism in women with femoral neck fracture.

Abnormalities in plasma vitamin D metabolites and an increased prevalence of osteomalacia have been described in elderly patients sustaining a fracture of the femoral neck. In order to investigate whether the plasma concentrations of the vitamin D metabolites are normal, and whether vitamin D deficient osteomalacia in patients with femoral fracture can be diagnosed using biochemical criteria alone, we have studied before and after 7 days of 40 micrograms oral 25-hydroxyvitamin D3 elderly patients admitted to hospital with a femoral fracture, elderly patients undergoing elective replacement of the femoral head and elderly control patients in hospital with no clinical evidence of bone disease. Plasma 25-hydroxyvitamin D (25(OH)D) and 24,25-dihydroxyvitamin D increased after 7 days of oral 25-hydroxyvitamin D3 to the same levels in the three groups, but in contrast to the controls there was no significant increase in plasma 1,25-dihydroxyvitamin D or radiocalcium absorption in femoral fracture and hip replacement patients. However, when femoral fracture patients were restudied 6-12 months after fracture, plasma 1,25-dihydroxyvitamin D increased after oral 25-hydroxyvitamin D3 to the same extent as it had in the control patients. We conclude that reduced calcium absorption due to low plasma 25(OH)D levels, i.e., vitamin D insufficiency is common in all elderly patients. Furthermore biochemical criteria for diagnosis of vitamin D-deficient osteomalacia are of very limited use at the time of fracture in elderly patients since there is a failure of production of 1,25 dihydroxyvitamin D which resolves within 6-12 months of the fracture. This failure makes the 1,25-dihydroxyvitamin D response to oral 25(OH)D an unreliable guide to the presence of vitamin D-deficient osteomalacia at the time of fracture. The abnormality in 1,25-dihydroxyvitamin D is also present in patients undergoing hip replacement surgery, and is therefore unlikely to be involved in the aetiology of femoral neck fracture. It may, however, contribute to the morbidity after fracture.

24,25-Dihydroxyvitamin D 3

Dose dependent response of symptoms, pituitary, and bone to transdermal oestrogen in postmenopausal women.

The effect of the plasma oestradiol concentration on climacteric symptoms, gonadotrophin release, and bone resorption was studied in three groups of postmenopausal women given 0.025 mg, 0.05 mg, or 0.1 mg transdermal oestradiol daily. There was a dose related reduction in symptoms, plasma follicle stimulating hormone concentration, and urinary calcium and hydroxyproline excretion. The relation of the response to plasma oestradiol values was similar for each variable with an initial large reduction and little change in response to increases in the plasma oestradiol concentration above 150 pmol/l (41 pg/ml). Hormone replacement therapy producing an effect equivalent to higher oestradiol concentrations is likely to increase the risk of side effects without conferring any additional benefit.

Administration, Cutaneous

Characteristics of antisera to antigenic forms of 1,25-dihydroxycholecalciferol.

Antisera to 1,25-dihydroxycholecalciferol were raised to 1,25-dihydroxycholecalciferol 25-hemisuccinate-bovine serum albumin, 1,25-dihydroxycholecalciferol 3-hemisuccinate-bovine serum albumin, 1,25-dihydroxycholecalciferol 3-hemisuccinate-porcine thyroglobulin and (5Z,7E)-(1S,3R)-1,3 dihydroxy-9,10-seco-24,25, 26,27-tetrakisnor-5,7,10(19)-cholestatrien-23-oic acid porcine thyroglobulin in rabbits. The antisera cross-reacted with a wide spectrum of vitamin D metabolites but their affinity was highest for 1,25-dihydroxycholecalciferol and some differentiated between ergo- and cholecalciferol metabolites. The presence of vitamin D binding protein and the pH of incubation markedly affected the sensitivity and specificity of antisera. A number of antisera were capable of measuring the normal plasma concentrations of vitamin D metabolites and their different affinities could be used for the measurement of 1,25-dihydroxyergocalciferol and 1,25-dihydroxycholecalciferol in plasma. None however were specific enough for the direct measurement of the metabolites in plasma. Immunisation increased the plasma concentration of endogenous 1,25-dihydroxyergo- and cholecalciferol in the animals.

Antigen-Antibody Complex