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Biomedical subjects

M Worsfold

Publications and source records attributed to M Worsfold.

At least 19 recordsLinked to original sources
PubMed2003

Radiological and biochemical resolution of nutritional rickets with calcium.

AIMS: To determine the response to oral calcium in Nigerian children with rickets. METHODS: In a teaching hospital in Western Nigeria, 26 children (13 boys, 13 girls, aged 2-5 years) with confirmed rickets received calcium lactate (2.7 g/day). RESULTS: Within one month of treatment leg pain was relieved and the children were more active. The mean x ray score improved from 3.3 at baseline to 1.7 at three months and 0.9 at six months (arbitrary scoring system, 0-6). Twelve cases were healed radiologically after six months, 11 others improved considerably, two showed no significant improvement, and a non-compliant patient was worse. There was progressive reversal of biochemical features. Median plasma alkaline phosphatase fell from 519 (range 178-1078) to 283 (209-443) IU/l (p = 0.04) in four months, while mean 1,25-dihydroxyvitamin D fell from 473 (251-1057) to 281 (155-481) pmol/l (p = 0.04), and mean plasma calcium increased from 2.26 (1.63-2.54) to 2.37 (2.06-2.54) mmol/l (p = 0.13). Parathyroid hormone fell from 5.3 (0.4-21.5) to 1.7 (0.45-7.4) pmol/l. Type I collagen carboxy terminal cross linked telopeptide was very high at baseline (20 (7.2-103) to 14 (11-24) micro g/l) (p = 0.03) and fell promptly to normal. CONCLUSION: Calcium supplementation alone effected healing of rickets in most of these Nigerian children and may provide sufficient treatment in this environment.

Calcium↗
PubMed1999

Age-related changes in body composition, hydroxyproline, and creatinine excretion in normal women.

We have made a cross-sectional study of relationships among age, whole body bone mineral content (WBBMC), and non-bone lean body mass (NBLBM) measured by dual energy X-ray absorptiometry (DXA), and daily excretion of hydroxyproline (OHP) and creatinine (Cr) in a group of normal women. WBBMC fell with age from the 6th decade, whereas NBLBM was almost constant. Creatinine excretion fell with age from the 5th decade until the 9th, to a much greater degree than NBLBM, reaching a nadir in the 8th decade. Daily excretion of hydroxyproline showed a peak in the 6th decade and fell moderately thereafter. The greater fall of creatinine compared with hydroxyproline resulted in rising OHP/Cr ratios with advancing age, in contrast to the pattern of hydroxyproline excretion. The use of creatinine as a correction for urine dilution or for lean body mass (LBM) in assays for markers of bone turnover must therefore be viewed with caution.

Absorptiometry, Photon↗
PubMed1997

Elevated collagen turnover in Nigerian children with calcium-deficiency rickets.

Calcium deficiency is a major etiological determinant of rickets in Nigerian children and is accompanied by undermineralization of the developing bone matrix which is composed largely of type I collagen. We have assessed types I and III collagen metabolism by measuring the circulating concentrations of teh N- and C-terminal pro-peptides (intact PINP and PICP) and the C-terminal telopeptide (ICTP) of type I collagen, and the N-terminal pro-peptide (PIIINP) of type III collagen in 94 healthy Nigerian children and in 44 children aged 1-5 years with active calcium-deficiency rickets. In active rickets the mean levels of the four collagen metabolites were approximately twofold higher than in the healthy children, despite a wide variation of individual values. Mean intact PINP was 812 +/- 279 versus 403 +/- 189 microg/liter; PICP was 573 +/- 265 versus 348 +/- 299 microg/liter; PIIINP was 16.8 +/- 8.6 versus 10.8 +/- 3.6 microg/liter, and ICTP was 28.4 +/- 17.2 versus 11.9 +/- 4.1 microg/liter (all P < 0.001), in rachitic and healthy children, respectively. Healthy children younger than 3 years had higher levels of all the collagen metabolites than those between 3 and 5 years (all P < 0.05). Alkaline phosphatase was greater in rickets than in the healthy group (P < 0.001) whereas mean osteocalcin levels were slightly lower (P = 0.009). 1,25(OH)2D correlated with all the collagen propeptides, but not with ICTP in the healthy children. No such correlations were found in rickets, where there was a poor inverse correlation between 1,25(OH)2D and ICTP. These data suggest that collagen turnover is elevated in cases of calcium-deficiency rickets, where vitamin D status is adequate, possibly indicating increased turnover of undermineralized osteoid.

Bone Development↗
PubMed1996

Plasma osteocalcin in healthy Nigerian children and in children with calcium-deficiency rickets.

Osteocalcin is an osteoblast-specific protein believed to be associated with events occurring during bone mineralization, which has been widely used clinically as an indicator of osteoblast function. Plasma osteocalcin concentrations (pOC) were studied in 94 (59 male, 35 female) healthy and 44 (21 male, 23 female) rachitic Nigerian children, all one to five years of age. The study was aimed at establishing a reference range for healthy Nigerian children determining any changes in plasma osteocalcin levels occurring in children with calcium-deficiency rickets. In the controls, pOC levels ranged from 3-89 ng/ml, with a mean value of 23 +/- 19 ng/ml. The values were higher in girls (29 +/- 21 ng/ml) than in boys (21 +/- 18 ng/ml), though not significantly. The controls had values consistent with other published pediatric ranges from Europe and North America. In the younger rachitic children (under 3 years) the mean pOC was lower than in the controls (P = 0.04) despite the much elevated plasma levels of 1,25(OH)2D. In the controls, pOC correlated with 1,25(OH)2D (r = 0.59, P = 0.003), alkaline phosphatase (r = 0. 22, P = 0.03), and inorganic phosphate (r = 0.27, P = 0.01). These correlations were lost in the rickets group. The findings in the controls confirm the known association between plasma 1,25(OH)2D and circulating osteocalcin levels, whereas the findings in the rickets group suggest that the stimulatory effects of 1,25(OH)2D on osteocalcin may depend on other permissive factors, such as normal circulating levels of calcium and phosphate.

Alkaline Phosphatase↗
PubMed1996

Etiology of rickets in Nigerian children.

We studied 26 Nigerian children with active rickets (13 boys, 13 girls), aged 1 to 5 years, and compared results of biochemical studies with those of healthy control subjects. The plasma 1,25-dihydroxyvitamin D level was elevated (568 +/- 317 pmol/L) and the 25-hydroxyvitamin D level was (36 +/- 28 mol/L) in the children with rickets compared with the control subjects (369 +/- 134 nmol/L and 69 +/- 22 nmol/L, respectively). The results suggest that rickets in Nigeria is largely the result of calcium deficiency and that vitamin D deficiency and possibly end organ resistance may be contributory factors.

Calcium↗
PubMed1996

Effects of low- and conventional-dose transcutaneous HRT over 2 years on bone metabolism in younger and older postmenopausal women.

The minimum dosage of transcutaneous hormone replacement therapy (HRT) able to exert protective effects on postmenopausal bone mass, especially in older women, is uncertain. This study investigates the effects of transcutaneous HRT at two different doses of oestradiol [Estraderm 25 and 50 (E25, E50)] over 2 years in 44 postmenopausal women younger than 67 years and 27 of 67 years and older. Circulating biochemical markers of bone and connective tissue turnover, collagen type I (intact PINP, PICP) and type III (PIIINP) propeptides and type I telopeptide (ICTP), osteocalcin (OC) and alkaline phosphatase (AP) were measured. The responses of the biochemical markers in all the groups were very similar, and most of the observed changes occurred within the first year of treatment. E25 had an effect on the bone markers similar to that of E50, and there was little difference in response according to the patient's age. PINP fell markedly after 1 year in all groups to about half the pretreatment level, with a smaller drop in the second year. PICP responded more variably, and mean values were little changed. There was a slight fall at the higher dose in the younger women, and also in the older women (whose baseline level was higher) on the lower dose. The correlation between PINP and PICP was 0.52 at pretreatment and 0.84 after 2 years of treatment. PIIINP showed no changes. OC and AP both fell in all groups by the first year, but less markedly than PINP. Their response was slightly less pronounced in the older women. ICTP fell marginally in the younger women, and only after 2 years, regardless of dose. Postmenopausal serum oestradiol levels increased after HRT and were associated with decreased binding globulin (SHBG) levels in all groups. After E25 patch application individual serum oestradiol levels were variable and peaked between 13 and 36 h with a median value of 83.8 pmol L-1. Our data suggest that low-dose transcutaneous HRT restores circulating oestradiol levels in postmenopausal osteopenic women of all ages as effectively as conventional-dose HRT and is associated with decreased circulating markers of bone and connective tissue turnover.

Administration, Cutaneous↗
PubMed1993

Plasma aluminium in a reference population: the effects of antacid consumption and its influence on biochemical indices of bone formation.

Aluminium is involved in the etiology of several complications of chronic renal failure and has been firmly established as having toxic effects on bone tissue. We have measured plasma aluminium together with serum osteocalcin, procollagen I C-terminal peptide and total alkaline phosphatase activity in healthy subjects and in a group of subjects who consumed aluminium-containing and non-aluminium containing antacid preparations, with normal renal function. Age-related healthy reference ranges for plasma aluminium are presented and the effects of chronic antacid consumption on plasma aluminium and biochemical markers of bone formation investigated. In 172 healthy subjects the mean plasma aluminium concentration was 4.4 +/- 2.9 micrograms L-1, men having a significantly greater circulating aluminium load than women (5.4 +/- 2.8 micrograms L-1 vs. 4.0 +/- 2.8 micrograms L-1 respectively (P = 0.0039)). Older men were found to have significantly higher plasma aluminium levels than younger men. Increased plasma aluminium was seen in subjects taking antacids although this was not associated with significant changes in most indices of bone formation.

Adult↗
PubMed1993

Anomalous rise of serum osteocalcin following desferrioxamine treatment in aluminium intoxication.

A patient with impaired renal function, severe osteomalacia and aluminium intoxication is described. In response to Desferal (desferrioxamine) treatment, serum osteocalcin rose 8-fold whereas serum alkaline phosphatase and procollagen I peptide levels changed little. Chromatographic separation showed that the measured osteocalcin coeluted with intact osteocalcin. The osteocalcin in the serum probably comes from the liberation of pre-existing osteocalcin from the bone, concomitant with aluminium mobilisation, rather than by stimulation of de novo synthesis.

Aluminum↗
PubMed1991

Bone mineral content in patients with rheumatoid arthritis: relationship to low-dose steroid therapy.

Bone mineral content (BMC) of the distal forearm was measured by single photon absorptiometry in 142 patients with rheumatoid arthritis (RA) of whom 27/54 men and 44/88 women received low-dose steroid therapy (less than 10 mg/day). To study the effect of steroid therapy a case-control analysis was undertaken in patients matched for age, sex and disease duration. Steroid therapy was associated with a reduced BMC in men (1.16 +/- 0.29 versus 1.32 +/- 0.23; P less than 0.05) and post-menopausal (0.76 +/- 0.24 versus 0.91 +/- 0.25; P less than 0.02) but not pre-menopausal women (1.1 +/- 0.28 versus 1.1 +/- 0.17). Symptomatic fractures were more common in steroid-treated patients than in those who had not received steroids (10/71 versus 2/71; P less than 0.05). Serum osteocalcin, an index of bone formation, was measured in 106 cases. It tended to be higher in patients with RA than in controls but the values observed in steroid and non-steroid RA groups did not differ significantly. We conclude that low-dose steroid therapy is associated with increased bone loss and numbers of fractures in patients with RA but this does not appear to be the result of a simple defect in bone formation.

Absorptiometry, Photon↗
PubMed1988

Serum osteocalcin and other indices of bone formation: an 8-decade population study in healthy men and women.

In a study of 435 healthy men and women aged 17-97 yr, serum osteocalcin and alkaline phosphatase were measured together with 99TcMDP retention in women. In women, serum osteocalcin falls to a nadir at 35-39 yr, and the mean then rapidly rises 2-fold to a plateau from 50-75 yr. 99TcMDP retention falls to a minimum at 40-45 yr and then rises steadily with increasing age. Serum alkaline phosphatase rises in an indeterminate fashion from 20-25 yr onwards. Osteocalcin in men fell until age 60-70 yr and hardly changed thereafter, whereas serum alkaline phosphatase reached a minimum at age 30-40 yr and thereafter rose with age, as in women.

Adolescent↗