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D J Hosking

Publications and source records attributed to D J Hosking.

At least 55 records · Page 3Linked to original sources
PubMed1998

Genetic and environmental factors affecting bone mineral density in large families.

This study assessed whether relatives with low bone mineral density (BMD) could be identified in five large families using historical, biochemical, and genetic markers for osteoporosis. Fifty of 65 relatives had their bone density and bone turnover markers measured, together with an assessment of their risk factors for osteoporosis. Only 33% (5/15) of siblings, 50% (6/12) of children and 43% (10/23) of nephews and nieces had entirely normal BMD. There was no difference in life-style risk factors for osteoporosis, history of previous fractures or body mass index between normal subjects and those with osteopenia or osteoporosis. Osteopenic individuals had a significantly higher than normal osteocalcin value. Within families, there was no clear association between BMD and any of the genetic markers (vitamin D receptor gene polymorphisms, COL 1A1 and COL 1A2 polymorphisms of the collagen gene), either alone or in combination. The addition of genetic markers to the other risk factors for low BMD did not improve the prediction of BMD. In conclusion, we suggest that the presence of osteoporosis in a first degree relative should be one of the clinical indications for bone density measurement as the individuals at risk would not be picked up by other methods.

Adult↗
PubMed1997

Spontaneous hypoglycaemia in a noninsulin-dependent diabetes mellitus patient with disseminated pancreatic carcinoma.

A 52-year-old-woman with non-insulin-dependent diabetes mellitus developed carcinoma of the pancreas and had a Whipple's resection performed. She required pancreatic exocrine supplements and insulin post-operatively. Five years later metastatic disease became apparent, and was accompanied by episodic spontaneous hypoglycaemia necessitating the cessation of insulin therapy. Hormonal analysis was performed, off insulin, at a time of hypoglycaemia (glucose 0.9 mmol l-1) and showed negligible insulin concentrations (< 2 mU l-1) but raised IGF-II together with low IGF-I concentrations (1.85 and 0.1 U ml-1, respectively). The association between diabetes and pancreatic carcinoma, and the pathogenesis of non-islet cell tumour induced hypoglycaemia (NICTH) are discussed.

Diabetes Mellitus, Type 2↗
PubMed1997

The contribution of bone densitometry to the diagnosis and treatment of osteoporosis.

OBJECTIVE: It has recently been proposed that a specialist osteoporosis service, including bone densitometry, should be made available to those most at risk in the UK population. The aim of this study was to evaluate such a service, and in particular the role of bone densitometry, in terms of its effect on the diagnosis of osteoporosis and clinical management of the disease. METHODS: A retrospective data abstraction study was performed to investigate the diagnosis and management of patients referred to the Metabolic Clinic, City Hospital Nottingham, with a potential diagnosis of osteoporosis. Hospital records were available for 117 patients, aged between 45 and 59, who had attended the Clinic in a given time period and undergone bone mineral density measurement. RESULTS: Forty-eight patients (41.0%) had osteoporosis of the lumbar spine. The final diagnosis of osteoporosis after attending the clinic was different from that on referral in a substantial proportion (62.6%) of cases. Only 48.9% of patients with spinal osteoporosis were identified by their referring doctor. The percentage of patients receiving treatment for osteoporosis increased from 34.2% to 72.6% after attending the clinic. CONCLUSIONS: Measurement of bone mineral density identifies cases of osteoporosis who would not otherwise be detected and as a consequence contributes to the proportion of patients receiving treatment after referral. The osteoporosis service provided by the Metabolic Clinic including measurement of bone mineral density was thus found to have a considerable impact on the diagnosis and treatment of patients with osteoporosis.

Absorptiometry, Photon↗
PubMed1997

Current diet does not relate to bone mineral density after the menopause. The Nottingham Early Postmenopausal Intervention Cohort (EPIC) Study Group.

The influence of dietary Ca on peak bone mass and on subsequent bone loss is controversial. Despite this an assessment of nutritional status is often included in the clinical evaluation of osteoporosis risk. To assess the value of this we investigated the relationship between current diet and bone mineral density (BMD) in 426 postmenopausal women, aged 45-59 years, who were enrolled into an international multi-centre trial of alendronate for the prevention of postmenopausal osteoporosis. BMD of the lumbar spine and proximal femur was measured on two occasions approximately 2 weeks apart by dual-energy X-ray absorptiometry. Serum osteocalcin was measured by immunoradiometric assay and serum 25-hydroxycholecalciferol by radioimmunoassay. Dietary assessment was performed by analysis of a 3 d unweighted dietary record, using Salford University's Microdiet software. BMD at both the lumbar spine and femoral neck correlated significantly with BMI, age, and average serum osteocalcin concentration. We therefore corrected for these variables in subsequent analyses. Dietary Ca intake ranged from 223 to 2197 mg/d (median 852 mg/d). Neither dietary Ca intake nor any other nutritional variable correlated significantly with BMD. There was a weak, but significant correlation between Ca intake and serum osteocalcin. We conclude that current diet does not correlate with BMD in early postmenopausal women. However, present diet may affect the rate of change of BMD, and this is supported by the finding of a significant relationship between dietary Ca and serum osteocalcin, a marker of bone formation rate.

Absorptiometry, Photon↗
PubMed1997

Changes in bone mineral density in patients with Paget's disease treated with risedronate.

OBJECTIVES: To study changes in bone mineral density (BMD) in patients with Paget's disease of bone treated with risedronate. METHODS: Whole body dual energy x ray absorptiometry (DXA) scans were carried out on 20 patients with Paget's disease treated with oral risedronate. DXA scanning was carried out at baseline and 11 months. Whole body bone mineral content (BMC) was measured. In addition, regions of interest were drawn around the skull, individual lumbar vertebrae, hemipelvis, femora, and tibiae to obtain BMD for these sites. An uncoupling index was also calculated as the area under the curve for serum alkaline phosphatase (ALP) divided by the area under the curve for hydroxyproline excretion (HYPRO) for the period of treatment. RESULTS: Median whole body BMC increased from 3057 g to 3156 g (p < 0.001) resulting from an increase in pagetic and non-pagetic BMD. From the analysis of regions of interest it was found that pagetic trabecular bone showed the largest increase in BMD. The pretreatment HYPRO and the uncoupling index were significantly related to the change in BMD for all pagetic sites for a patient (r = 0.65, p < 0.01 and r = 0.57, p < 0.05 respectively). CONCLUSION: Bisphosphonate treatment of Paget's disease results in an increase in BMD of pagetic bone without redistribution of mineral from non-pagetic bone. The remodelling space and extent of uncoupling are significantly related to increases in BMD at pagetic sites.

Absorptiometry, Photon↗
PubMed1996

Is macrosomia associated with poor glycaemic control in diabetic pregnancy?

The study aimed to determine the influence of glucose control during pregnancy on the incidence of macrosomia in the infants of mothers with insulin-dependent diabetes. The prevalence of macrosomia was determined in pregnancies of all such women attending the City Hospital Nottingham, between July 1987 and July 1993, where it is policy for diabetic patients to aim during pregnancy for preprandial capillary glucose levels of less than 6.0 mmol I-1, and postprandial glucose levels of less than 8.0 mmol I-1. Macrosomia was defined as a birthweight greater than 90th centile using a computer model which takes into account all the major determinants of birthweight. Twelve of 29 infants were macrosomic, which is greater than expected (p < 0.01). During pregnancy there was no difference in mean seven point glucose profiles between those mothers with normal weight babies and those with macrosomia, but fructosamine levels at booking were significantly higher in the latter 2.5 (1.9-2.9) vs 2.2 (1.2-3.0); p < 0.05. These data confirm other studies and suggest that the incidence of macrosomia may be reduced by tighter control of diabetes at conception and in the first trimester, but to a lesser extent during later pregnancy.

Blood Glucose↗
PubMed1996

Biochemical and radiologic improvement in Paget's disease of bone treated with alendronate: a randomized, placebo-controlled trial.

PURPOSE: The potent bisphosphonates offer great promise in the management of Paget's disease of bone, but are currently available only as parenteral preparations in most countries. There is a need for a well-tolerated, oral therapy. Furthermore, none of the currently available therapies have been rigorously demonstrated to heal the lytic bone lesions characteristic of this condition. Alendronate is a potent new oral aminobisphosphonate that has shown promising effects on Paget's disease in preliminary studies. METHODS: We report a double-blind, randomized comparison of oral alendronate 40 mg/day and placebo over 6 months in 55 patients with Paget's disease. Efficacy was determined from measurements of biochemical indices of bone turnover (serum alkaline phosphatase and urine N-telopeptide) and blinded radiologic assessment of lytic bone lesions. RESULTS: N-telopeptide excretion declined by 86% and serum alkaline phosphatase by 73% in patients receiving alendronate, but remained stable in patients receiving placebo (P < 0.001 between groups for both indices). Responses were similar whether or not patients had previously received bisphosphonate treatment. Alendronate treatment normalized alkaline phosphatase in 48% of patients. Forty-eight percent of alendronate-treated patients showed radiologic improvement in osteolysis whereas in the placebo group only 4% improved (P = 0.02 for between-groups comparison). No patient in either group showed worsening of osteolysis. Bone histomorphometry indicated that alendronate tended to normalize turnover indices. There was no evidence of abnormal mineralization in bone biopsies taken from 12 alendronate-treated subjects. The treatment was well tolerated. CONCLUSION: Oral alendronate appears to be a safe and effective therapy for Paget's disease and results in healing of lytic bone lesions.

Administration, Oral↗
PubMed1996

Fluoride pharmacokinetics and changes in lumbar spine and hip bone mineral density.

Debate about the use of fluoride for the treatment of vertebral osteoporosis has centered not only on whether fluoride treatment decreases vertebral fractures, but also the interindividual vertebral bone mineral density (BMD) response, the potential for nonvertebral fractures, as well as side effects and tolerability. These effects may be dose dependent and, in this study, we examine the pharmacokinetics of sodium monofluorophosphate (MFP) in osteoporotic patients and relate this to changes in BMD. Plasma fluoride absorption curves were measured from 0 to 6 h after ingestion of MFP at baseline and during long-term dosing in 21 patients with vertebral osteoporosis (T scores < or = 2). BMD was measured at baseline and at 12 months at the lumbar spine (LS), femoral neck (FN), trochanter, and Ward's triangle. We found that fluoride elimination was inversely related to creatinine clearance. LS BMD increased from a median of 0.77 g/cm2 (range 0.69 to 0.99) at baseline to 0.88 g/cm2 (0.75 to 1.13) (p < 0.001) after 12 months. This equates to a median increase of 12% (range -1.2 to 37). Median femoral neck BMD decreased from 0.75 g/cm2 (0.62 to 0.94) at baseline to 0.69 g/cm2 (0.62 to 0.92) (p = 0.13) after 12 months. This equates to a decrease of -2% (-19 to 10). BMD at the other hip sites also decreased slightly. Changes in LS and FN BMD were not significantly related (r = 0.28, p = 0.29). The various pharmacokinetic parameters measured were not related to changes in LS BMD; however, there was an inverse relationship between trough fluoride concentration during long-term dosing and change in FN BMD. Further studies are required to see if this relationship can be used to monitor osteoporotic patients treated with fluoride and prevent significant decreases in FN BMD and possibly fractures at this site.

Adult↗
PubMed1996

A multicenter study of the influence of fat and lean mass on bone mineral content: evidence for differences in their relative influence at major fracture sites. Early Postmenopausal Intervention Cohort (EPIC) Study Group.

We examined the relative influence of fat and lean mass on bone mineral content (BMC) among 1600 early postmenopausal women aged 45-59 y from four geographical locations (Nottingham, United Kingdom; Portland, OR; Honolulu; and Copenhagen). Bone sites investigated included the major fracture sites: hip, spine, and radius. Body weight had strong associations at all skeletal sites examined [BMC differences of 4-6% per interquartile range (IQR) of weight]. Associations with the fat and lean components of weight were more variable. The BMC differences per IQR of lean mass were 5-7% at the hip sites, 3% at the spine, and 2% at the radial sites. The greater differences for lean mass at the hip may reflect the high physical mobility and muscular activity of this site. The BMC differences per IQR of fat mass were 4-6% at the hip sites, 4% at the spine, and 5% at the ultradistal radius. These results suggest that low fat mass or low lean mass, particularly at the extremes, may adversely affect the major fracture sites. The bone sites with the greatest differences for fat mass were the most highly trabecular sites. With only a few exceptions, the associations of BMC with fat mass and lean mass were similar in direction and comparable in magnitude across the four geographic locations. We conclude that both fat and lean mass have independent influences on bone mass, but that their relative influence may vary by bone site depending on the trabecular content, physical mobility, and muscularity of the site.

Adipose Tissue↗
PubMed1996

Calcium homeostasis in pregnancy.

The demands of fetal growth lead to an adaptation of maternal homeostasis in order to provide the required calcium from enhanced intestinal absorption rather than from mobilization of maternal skeletal reserves. In large part this adaptive process depends on the interrelationship between PTH and 1,25(OH)2D which shows quantitative rather than qualitative changes from the non-pregnant state. In contrast the maintenance of fetal mineral homeostasis largely depends on PTHrP which regulates active placental calcium transfer and the calcium fluxes across the kidney and bone. The major source of PTHrP is the fetal parathyroid gland although some is provided by the placenta. It may be this latter component which passes into the maternal circulation where it may play a role in calcium homeostasis by acting through the PTH receptor.

Biological Transport↗
PubMed1995

Quantitative bone scintigraphy in the management of monostotic Paget's disease of bone.

OBJECTIVE: To assess the use of quantitative bone scanning (QBS) in the monitoring of patients with intravenous pamidronate-treated symptomatic monostotic Paget's disease of bone in whom biochemical markers of bone turnover are relatively normal. METHODS: QBS was performed in 9 patients and the results were expressed as a ratio, obtained by comparing isotope uptake at an affected and a control (unaffected) site. RESULTS: Serum alkaline phosphatase levels were normal in 7 of the 9 patients and changed minimally with treatment. The median QBS ratio was 2.72 (range 1.69-24.6) at baseline and 1.49 (range 0.63-4.18) posttreatment (P = 0.008). The median symptom score decreased with treatment, but QBS ratios provided the only objective measure of disease activity by which response to pamidronate therapy could be judged. CONCLUSION: QBS may be a useful technique for evaluating the effects of treatment in patients with Paget's disease of bone.

Adult↗
PubMed1995

Comparison of methods of assessing response of Paget's disease to bisphosphonate therapy.

Bisphosphonates have been shown to be effective in suppressing the elevated bone turnover found in Paget's disease of bone. In theory, the major determinants of post-treatment bone turnover are the initial disease activity and the rate of decline in bone turnover with therapy. In the present study, we examined the rate of decrease of alkaline phosphatase and hydroxyproline (expressed as a half-life) and showed this to be superior to percentage changes in bone turnover as a marker of response. The combination of pre-treatment alkaline phosphatase and the alkaline phosphatase half-life and pre-treatment hydroxyproline and the hydroxyproline half-life were the best models to predict post-treatment bone turnover (multiple r = 0.75, r2 = 0.56, p < 0.0001; and r = 0.71, r2 = 0.51, p < 0.0001, respectively). In addition, measurement of the half-lives of these markers of bone turnover may allow prospective changes to be made during treatment so that maximal disease suppression can be achieved.

Alkaline Phosphatase↗
PubMed1993

Determinants of remission of Paget's disease of bone.

Bisphosphonates are a safe and effective treatment for Paget's disease of bone, but little information is available about the factors influencing the duration of remission so obtained. We assessed 60 patients with Paget's disease treated with disodium pamidronate (APD). The mean duration of remission was 9.5 months (range 3-25). The major influences were the initial pretreatment alkaline phosphatase (ALP; r = -4.6, p < 0.0001), minimum posttreatment ALP (r = -0.51, p < 0.0001), and the rate of response of bone turnover to the first dose of APD (r = 0.61, p < 0.0001). Multiple linear regression showed that the initial response to treatment was the most significant influence. Also, despite a minimum ALP within the normal range, the duration of remission varied considerably (4-25 months). This may be due to the difficulties in applying a population-based normal range to individuals.

Aged↗
PubMed1993

Effects of corticosteroids on bone turnover.

The pathophysiology of corticosteroid-induced osteoporosis is complex, but centres around a primary inhibition of osteoblastic activity compounded by the effects of secondary hyperparathyroidism. The preservation of the microanatomy of bone in the early stages of the disease, coupled with strategies to prevent the emergence of secondary hyperparathyroidism, and the potential availability of osteoblastic stimulants offer the hope of minimizing this important side-effect of corticosteroid therapy.

Adrenal Cortex Hormones↗
PubMed1993

Abnormalities in osteoclast precursors and marrow accessory cells in Paget's disease.

Paget's disease of bone is characterized by increased numbers of abnormal osteoclasts. To determine if osteoclast precursors were increased or abnormal in this disease, we examined CFU-GM, the committed granulocyte-macrophage progenitor and the most likely precursor for osteoclasts. In cultures of unfractionated marrow mononuclear cells, CFU-GM colony formation was significantly increased in Paget's marrow cultures compared to that in normal cells (356 +/- 44 vs. 271 +/- 15/10(5) cells; P < 0.05). However, when we enriched hematopoietic precursors from Paget's and normal marrow samples using an antibody that recognizes the CD34 antigen present on most hematopoietic precursors, we found that similar numbers of CFU-GM colonies were formed (87 +/- 13/10(4) cells plated vs. 83 +/- 13). Coculture experiments with highly purified hematopoietic precursors (CD34+ cells) and nonhematopoietic marrow accessory cells (CD34- cells) revealed that the growth of Paget's precursors was significantly enhanced above expected levels by normal or Pagetic CD34- cells (P < 0.05). CFU-GM colony formation was also significantly enhanced when normal CD34+ cells were cocultured with Pagetic, but not with normal, CD34- cells. In addition, CFU-GM colony-derived cells from Paget's patients were hyperresponsive to 1,25-dihydroxyvitamin D3 and could form osteoclast-like multinucleated cells with 1,25-dihydroxyvitamin D3 concentrations one tenth of that required for normal multinucleated formation (10(-11) vs. 10(-10) M). These data suggest that osteoclast precursors may be abnormal in Paget's disease, and other cells in the Pagetic marrow microenvironment may further enhance the growth and differentiation of these abnormal precursors.

Antigens, CD↗