Biomedical subjects
Publications and source records attributed to A Fairney.
Vitamin D deficiency and primary hyperparathyroidism (PHPT) are relatively common disorders. The coexistence of these conditions should be considered, as depletion of vitamin D may alter the clinical expression of autonomous parathyroid disease. We report details of a vitamin D deficient patient in whom replacement therapy led to the unmasking of occult PHPT.
Patients with cystic fibrosis (CF) have low bone mineral density (BMD). The clinical relevance of this is not clearly established. The aim of this study was to determine the prevalence of low BMD and vertebral deformities in CF adults with varied disease severity. One hundred and seven patients (58 men) aged 18-60 years underwent dual-energy X-ray absorptiometry scanning of the lumbar spine and hip, radiology of the spine and biochemical studies. Thirty-eight percent had a Z-score of < -1, with 13% having Z-scores < -2. Seventeen percent had evidence of vertebral deformity on radiography, mostly in the thoracic spine. Thirty-five percent reported past fractures, of which 9% were rib fractures. Percent predicted forced expiratory volume in 1 second (FEV1) and the amount of daily physical activity were positively related to BMD. The number of intravenous antibiotic courses in the previous 5 years was negatively related to BMD. Patients with a history of rib fracture and CF-related diabetes had significantly lower femoral neck BMD (p < 0.02). The median serum 25-hydroxyvitamin D was 28 nmol/l, with 36% of patients having levels below 25 nmol/l despite vitamin D supplementation. Forty-four percent had raised levels of urinary pyridinium crosslinks (NTx). In conclusion, fragility fractures and hypovitaminosis D occur commonly in adult patients with CF. Low BMD occurs in patients with more severe disease and significantly relates to FEV1, infective exacerbations and daily energy expended in physical activity.
Hypogonadism is a recognised cause of osteoporosis in men. When patients with advanced prostate cancer are treated with luteinising hormone releasing hormone (LHRH) agonist analogues their circulating testosterone levels decline and these patients may develop fractures.We have undertaken a cross-sectional study on a cohort of patients treated with goserelin (n=41) and compared their bone density and bone turnover with patients with prostate cancer not on goserelin and elderly patients living in the community.There was no difference in bone density between the patients on treatment and those living in the community and there was a similar incidence of osteoporosis (50 and 42%, respectively). The bone marker measurements were higher in the treated patients: urine N-telopeptide (NTX) 80.1 (9) (mean (s.e.)) BCE/mmol, compared to 30.1 (2.9), P<0.001 in elderly patients; and bone alkaline phosphatase 41.9 (6.1) u/l in treated patients and 20.7 (1.5) in untreated prostate cancer patients, P<0.002. Patients on treatment with radionuclide scan evidence of metastases did not have higher bone marker values than those with negative scans.As increased bone turnover and low bone density are associated with enhanced risk of osteoporotic fractures, we suggest that patients on LHRH agonist analogues should receive advice and possibly anti-bone resorptive treatment with bisphosphonates to prevent further bone loss and fractures.Prostate Cancer and Prostatic Diseases (2001) 4, 161-166.
Bisphosphonates such as etidronate and alendronate are widely accepted as effective agents for the treatment of osteoporosis. However, some physicians find the choice of which one to use in different patients, and the comparative magnitude of response, unclear. Fifty postmenopausal women with osteoporosis [group 1: 27 women who had received 3 years of previous cyclical etidronate treatment, mean age 70.5 years, bone mineral density (BMD) mean T-score lumbar spine (LS) -3.58 and femoral neck (FN) -2.51; group 2: 23 women who had not previously received cyclical etidronate treatment, mean age 73.7 years, BMD mean T-score LS -3.65 and FN -2.96] were treated with 10 mg alendronate daily, to determine whether pretreatment with etidronate affected the response to alendronate, and whether patients who did not respond to etidronate, responded to alendronate. There was a significant increase in LS BMD after 2 years of treatment with alendronate compared with baseline (group 1: 7.84%, p<0.001; group 2: 6.69%, p<0.001), but there was no statistical difference between the groups. In the group 1 patients there was a significant difference between the initial response (at the LS BMD) to 2 years of cyclical etidronate (1.86%) and later response to 2 years of alendronate (7.84%) (p<0.0001). The 10 patients who did not respond at the LS to etidronate alone, showed a significantly better response (mean BMD change +6.3%) when subsequently treated with alendronate (a net difference of 9.3%, p=0.002). In 15 patients who did not respond at the FN to etidronate alone, the mean response to alendronate was +0.96% (a difference of 7%, p= 0.004). This study shows that pretreatment with 3 years of cyclical etidronate is not detrimental to the subsequent LS BMD response to alendronate. There is evidence that alendronate produced a greater bone density response than etidronate, and patients who did not respond to etidronate with an increase in LS bone density, subsequently did so following alendronate.
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We have evaluated three commercial assays for collagen cross-links, two urine assays and a recently developed serum assay, as markers of bone turnover in 30 postmenopausal women with osteoporosis during their first year of treatment with the anti-resorptive drug alendronate. Before treatment, urine free deoxypyridinoline crosslinks (Dpd), urine N-telopeptide crosslinks (NTx) and serum C-telopeptide (CTx) values were within postmenopausal reference ranges. After 3 months' treatment the decrease in NTx and CTx was greater than that of Dpd (-50%, P < 0.0001 and -48%, P < 0.0001, compared with -11%, NS), as it was after 6 months (-51%, P < 0.0001, and -57%, P < 0.0001, compared with -19%, P < 0.01). The decrease in resorption markers after 6 months was significant in 23% (Dpd), 66% (NTx) and 66% (CTx) of individuals. Neither baseline resorption marker values nor the per cent change after 6 months' therapy correlated with bone mineral density change (BMD) at either lumbar spine or femoral neck after one year's therapy, except baseline Dpd and lumbar spine BMD (P < 0.01). We conclude that NTx and serum CTx were more sensitive markers of bone turnover suppression by alendronate, but only baseline Dpd was useful in the prediction of individual bone density response after one year.
An open study over 4 yr has been conducted to determine the efficacy of cyclical etidronate treatment in patients from the community, with osteoporosis and in those at risk who attended an osteoporosis clinic; and to clarify whether bone remodelling returns to baseline values and bone mass is maintained after completion of a 3 yr course of treatment. One hundred and fifteen female patients, with and without osteoporotic fractures (n = 62 and 53, respectively), who were unsuitable for, or declined, hormone replacement therapy, received 3 yr cyclical etidronate treatment (400 mg etidronate disodium for 14 days followed by 500 mg elemental calcium for 76 days repeated in 3-monthly cycles) and 1 yr treatment-free follow-up. There was an overall increase in lumbar spine bone density (patients without fractures 2.6%, P < 0.001; with fractures 4.3%, P < 0.01) with minimal change at the femoral neck. The serum concentration of bone formation markers (osteocalcin and bone alkaline phosphatase) fell in response to treatment to a nadir at 6/12 (75 and 83% of baseline, respectively; P < 0.001). A cohort of patients (n = 29), 14 without fractures and 15 with fractures, was studied in more detail. After completion of treatment in the following treatment-free year, there was a resurgence of bone turnover (osteocalcin and bone alkaline phosphatase 117 and 122% of baseline, respectively; P < 0.05 and P < 0.01) with some evidence of maintenance of bone mass already gained. There is no evidence of persistent suppression of bone turnover after completion of treatment.
We have evaluated two commercial assays for serum bone specific alkaline phosphatase (bALP) as a marker of bone turnover in a group of 35 postmenopausal women with osteoporosis during their first year of treatment with the anti-resorptive drug, alendronate. The immunoradiometric assay (bALP-I) measured protein mass, whereas the immunocapture assay (bALP-E) measured activity. Before treatment, bALP values with both methods were within the postmenopausal reference ranges. Treatment with alendronate produced a decrease in bALP after 3 months, reaching a plateau after 6 months: for bALP-I a mean change of -34%, (P < 0.0001), bALP-E, -19% (P < 0.001), and total ALP, -19% (P < 0.0001). The decrease was significant in 53% (bALP-I) and 31% (bALP-E) of patients. The ratio of serum bALP-E/bALP-I in patients was not constant but rose after therapy with alendronate. Neither baseline bALP, nor the per cent change in bALP after 6 months, correlated with bone mineral density (BMD) change after 1 year at either lumbar spine or femoral neck. We conclude that bALP-I appeared to be a more sensitive marker of the suppression of bone turnover by alendronate than did bALP-E, but that neither was useful in the detection of osteoporosis, nor the prediction of individual BMD response to alendronate therapy.
OBJECTIVE: Short-term GH replacement in hypopituitary adults increases bone turnover; data on the consequences of longer-term GH treatment are limited. We report on the effects of 12-18 months of GH replacement treatment with biosynthetic human GH on bone metabolism and bone mass in hypopituitary adults. DESIGN: Patients were studied before and after GH treatment for 12 months (n = 11) and 18 months (n = 27) respectively in an open trial. GH dose was 0.04 +/- 0.01 IU/kg daily. MEASUREMENTS: Plasma calcium, phosphate and intact PTH concentrations, 24-hour urinary calcium excretion, 3 markers of bone formation (total alkaline phosphatase, osteocalcin and procollagen 1 carboxy terminal peptide (P1CP)) and serum concentration of carboxyterminal cross-linked telopeptide of type 1 collagen (ICTP), as a marker of bone resorption, were measured at 6-month intervals. Lumbar spine and total body bone mineral mass was measured by dual-energy X-ray absorptiometry. RESULTS: Small increases were observed in plasma calcium and phosphate concentrations at 12 months of GH therapy but the differences at 18 months were not statistically significant. Serum intact PTH concentration did not change. Plasma total alkaline phosphatase increased significantly on GH from 75 +/- 26 to 92 +/- 30 (P < 0.01) and 85 +/- 31 U/I (NS) at 12 and 18 months respectively. Serum osteocalcin increased from 6.5 +/- 3.7 to 15.7 +/- 6.2 (P < 0.0001) and 16.6 +/- 5.7 micrograms/I (P < 0.001) at 12 and 18 months respectively and P1CP increased significantly from 106.0 +/- 47.3 micrograms/I to 165.5 +/- 95.3 (P < 0.0001) and 177.2 +/- 72.2 micrograms/I (P < 0.01) at 12 and 18 months respectively. Plasma ICTP concentration increased also from 3.4 +/- 1.8 to 7.3 +/- 3.4 (P < 0.0001) and 7.0 +/- 2.7 micrograms/I (P < 0.003) at 12 and 18 months of GH therapy respectively. No significant change was observed in total body or lumbar spine bone mass, over the 18 months of GH treatment CONCLUSIONS: Replacement therapy with GH in hypopituitary adults for 6-18 months produced a sustained increase in bone turnover (both formation and resorption). Bone mass was maintained but did not increase over the study period.
OBJECTIVE: The importance of growth hormone (GH) for normal skeletal growth in childhood and adolescence is well established but much less is known about its action on the adult skeleton. We therefore wished to investigate the effects of replacement treatment with biosynthetic human GH in hypopituitary adults on aspects of calcium homeostasis, bone metabolism and bone mineral mass. PATIENTS: Forty hypopituitary adults (21 females and 19 males; aged 19-67 years). DESIGN: A prospective randomized double-blind placebo-controlled trial lasting for 6 months. PROTOCOL: Following baseline assessments, GH was given in a daily dose of 0.02-0.05 IU/kg body weight subcutaneously (or a placebo (P)) at bedtime. Patients were reviewed at 1, 3 and 6 months. MEASUREMENTS: Plasma calcium, phosphate and total plasma alkaline phosphatase were measured at 0, 1, 3 and 6 months. Serum insulin like growth factor I (IGF-I), osteocalcin, procollagen 1 carboxyterminal peptide (P1CP) and intact parathyroid hormone (PTH) level, 24-hour urinary calcium and creatinine excretion were all measured at 0 and 6 months. Bone mineral density of total body and lumbar spine was also measured by dual energy X-ray absorptiometry at 0 and 6 months in 12 patients on GH and 14 on placebo. RESULTS: Thirty-eight patients completed the study (18 on GH, 20 on placebo). Serum IGF-I increased significantly on GH treatment (mean +/- SD) (GH: 276 +/- 197 vs P: 88 +/- 50 micrograms/l, P < 0.0001 at 6 months). Plasma calcium increased slightly but significantly in the GH-treated group (2.23 +/- 0.11-2.29 +/- 0.11 mmol/l, P < 0.05). At the end of the study, plasma calcium was however similar on GH and placebo (GH, 2.29 +/- 0.11; P, 2.26 +/- 0.09 mmol/l). Plasma phosphate increased on GH (GH: 1.02 +/- 0.23-1.32 +/- 0.19; P: 0.99 +/- 0.16-0.96 +/- 0.12 mmol/l over the 6 months of treatment, P < 0.001). There was no significant change in the urinary calcium excretion on GH therapy. Plasma total alkaline phosphatase, osteocalcin and P1CP were significantly higher on GH than P at 6 months (alkaline phosphatase: GH: 104 +/- 32 vs P: 69 +/- 32 U/l, P < 0.01, osteocalcin: GH: 17.2 +/- 8.0 vs P: 5.3 +/- 3.2 micrograms/l, P < 0.001 and P1CP: GH: 207 +/- 152 vs P: 93 +/- 31 micrograms/l, P < 0.01). There was no difference in the intact parathyroid hormone level (GH: 31 +/- 14 vs P: 31 +/- 15 ng/l, NS). No significant change was observed in bone mass after 6 months of GH treatment, either in total body bone mineral content or in the lumbar spine. CONCLUSION: In this large study, GH replacement in hypopituitary adults for 6 months increased bone turnover but did not affect bone mineral content. Longer-term studies are required to assess further any effect on bone mass.
Abnormalities of calcium homeostasis are a recognized feature of end-stage renal disease. The treatment of choice is renal transplantation, but this does not always result in normalization of the biochemical profile. Persistent hypercalcaemia is well documented and our study was undertaken to investigate the status of the calcium regulating hormones in renal patients post-transplantation. Serum calcium, parathyroid hormone, 1,25-dihydroxyvitamin D (1,25(OH)2D) and osteocalcin concentrations were measured in post-transplant patients. Twenty per cent of the patients had subnormal 1,25(OH)2D concentrations while 55% had biochemical evidence of hyperparathyroidism but only 5% were hypercalcaemic. Time elapsed since transplantation was not correlated with any of the analytes investigated and there was no relationship between persistent impairment of renal function and abnormalities of calcium homeostasis.
A study has been undertaken to document in detail some of the changes that occur following parathyroidectomy in chronic renal failure patients. In an attempt to predict more precisely the timing of the post-operative hypocalcaemia, serum parathyroid hormone (PTH) concentrations were measured in six patients with renal osteodystrophy undergoing subtotal parathyroidectomy [5] and total parathyroidectomy [1]. The values obtained were related to post-operative changes in serum calcium and albumin concentrations. The intact-PTH concentration in serum was shown to decline rapidly post-operatively while the C-terminal PTH followed a more gradual course. Neither total nor ionised serum calcium concentrations exhibited a correspondingly dramatic fall after parathyroidectomy and the serum albumin concentration remained unaltered.
Studies of osteocalcin in the serum and synovial fluid of patients with rheumatoid arthritis (RA) and osteoarthritis (OA) showed the presence of significant amounts of osteocalcin in synovial fluid and that the values in RA synovial fluid were significantly lower than in OA synovial fluid. In addition, the osteocalcin in OA synovial fluid bound almost completely to hydroxyapatite, whereas a significant proportion of the osteocalcin in RA synovial fluid did not. These studies suggest that patients with severe RA produce low amounts of active osteocalcin and higher than expected amounts of inactive osteocalcin in the synovial fluid. They provide some evidence that osteoblast function may be abnormal in the osteoporosis of RA.
The hypothesis that sunlight may induce the enzymes involved in the vitamin D pathway has been tested by comparing the ability to synthesize vitamin D3 and its 25 hydroxy metabolite (25-OHD) in 2 groups of male volunteers resident at the British Antarctic base at Rothera Point (67 degrees 34'S.). One group endured the UV depleted winter and the other group received regular phototherapy throughout the winter. Both groups then received a course of 14 days phototherapy in October (Southern Hemisphere spring). The group receiving regular phototherapy had a trend towards a higher level of serum 25-OHD, and the October phototherapy course produced a further small increase in serum 25-OHD values. In the previously non irradiated group the October phototherapy produced a much larger increase in serum 25-OHD so that they attained the previously higher values of the pre-iradiated group. There was a negative correlation between the pre October phototherapy serum concentration of 25-OHD and the subsequent increment (r-0.78, p less than 0.01) but no relationship between the serum 25-OHD and D3 after phototherapy. These results provide evidence against the existence of enzyme induction of vitamin D 25 hydroxylase by light.
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1. Studies of serum 25-hydroxy-vitamin D (25-OHD) in the Antarctic have been undertaken in husky dog, seal and penguin and compared to man. 2. Husky dogs showed a reversal of the expected seasonal variation of serum 25-OHD with maxima in June when the hours of bright sunshine and amount of u.v. -B radiation were lowest. 3. Values for random serum 25-OHD values in seals showed large interspecies differences, the values for Weddell seals being significantly greater than for Crabeater seals (P less than 0.01). 4. Penguin sera showed low concentrations of serum 25-OHD with no evidence of a response to prolonged exposure to sunlight.
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A competitive protein-binding assay for 25-hydroxy vitamin D (25-OHD) in saliva has been established by adaptation of that previously described for 25-OHD in serum (Fairney et al. 1979). Random values of salivary 25-OHD in patients attending hospital for venesection showed a wide range of results (105-1000 pg/ml, n 55). These values corresponded to 1.2% of the total serum values with which they showed a significant relation (r 0.45, P less than 0.001). There was no relation between salivary 25-OHD and measured serum free 25-OHD in eighteen pairs of saliva and serum studied. Studies in two individuals showed that salivary 25-OHD values varied throughout the day and that a vitamin D load (19.5 micrograms), given as pickled herrings at lunch, produced a marked rise in 25-OHD values 5-8 h later. Diurnal profile studies of salivary 25-OHD in Caucasian and Asian 11-year-old male schoolchildren showed lower values in Asian children eating a vegetarian diet, and a significant variation with time and ethnic group (P less than 0.001). It is concluded that 25-OHD is present in saliva and that the values vary throughout the day. The values obtained may relate to dietary intake of vitamin D and the subject's ethnic origin.