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D J Hosking

Publications and source records attributed to D J Hosking.

At least 73 records · Page 4Linked to original sources
PubMed1993

Acute changes in calcium homeostasis during treatment of primary hyperparathyroidism with risedronate.

We administered risedronate, a potent oral bisphosphonate, to patients with mild primary hyperparathyroidism in order to 1) determine if we could normalize the serum calcium concentration in the short term, and 2) analyze changes in the homeostatic mechanisms responsible for maintaining hypercalcemia in this patient population. When administered for 7 days, risedronate reduced fasting serum calcium concentrations without significant toxicity in patients with primary hyperparathyroidism. The decrease in serum calcium was accompanied by evidence of inhibition of bone resorption, as assessed by measurement of urinary hydroxyproline, increased serum immunoreactive PTH concentrations, enhanced renal tubular reabsorption of calcium, and a progressive decrease in serum alkaline phosphatase. Serum PTH was partially suppressed by an oral calcium load in untreated patients as well as in patients treated with risedronate. Although patients treated with risedronate had normal fasting serum calcium levels, serum calcium values in these normocalcemic patients were labile after oral ingestion of calcium. After daily calcium intake of 2 g, serum calcium levels in risedronate-treated patients were similar to those in untreated patients with primary hyperparathyroidism, suggesting that there are likely to be fluctuations in serum calcium in risedronate-treated patients with normal fasting serum calcium during postprandial periods. These studies show that risedronate lowers fasting serum calcium during short term treatment. However, further studies are required to determine whether the lability in serum calcium in these patients after an oral calcium load has clinical significance, and whether longer term treatment would maintain serum calcium in the normal range.

Administration, Oral↗
PubMed1993

Drugs used in the treatment of metabolic bone disease. Clinical pharmacology and therapeutic use.

Osteoporosis is the most important metabolic bone disease and places an increasing burden on the healthcare system. The condition can be prevented by the early introduction of hormone replacement therapy. The role of bisphosphonates in achieving the same result is being actively explored. The attraction of preventing bone loss is that it preserves the micro-architecture of bone, and therefore its mechanical integrity. The great problem of treating the established condition is that substantial bone loss is accompanied by architectural disintegration. Replacing lost bone may not necessarily restore mechanical integrity and protect against fractures. The management of Paget's disease has been quite revolutionised by the introduction of the bisphosphonates. The condition is a result of a primary increase in osteoclastic bone resorption which can be corrected by bisphosphonates, with considerable symptomatic improvement. The increasing potency and safety margin of the newer agents has meant that the threshold for treatment has fallen. There is now potential for long term control of bone turnover with the hope of preventing late complications. Hypercalcaemia of malignancy is usually the result of both increased bone destruction and decreased urinary calcium excretion. These two components of hypercalcaemia demand different approaches to management. The general availability of an ever-expanding range of increasingly potent bisphosphonates has resulted in a dramatic improvement in the treatment of increased bone resorption associated with malignancy. Many types of tumour, either directly or indirectly, compromise the ability of the kidney to eliminate a calcium load derived from increased bone destruction. Calcitonin is the only agent which is currently available to counter this process.

Calcitonin↗
PubMed1992

Bisphosphonate space measurement in Paget's disease of bone treated with APD.

The bisphosphonate space (BPS) is a quantitative measurement of skeletal uptake of 99mTc-HMDP. We measured BPS in 36 patients with Paget's disease of bone, both before and 6 months after treatment with intravenous APD (disodium pamidronate) infusions. BPS fell after treatment, but proportionally less than serum alkaline phosphatase (ALP) and fasting urinary hydroxyproline/creatinine (HYPRO). There was no dose-response relationship between the dose of APD given and the percentage reduction in ALP and HYPRO at 6 months. Log dose of APD/pretreatment BPS, however, predicted the percentage reduction in ALP and HYPRO very well, and from the respective regression equations it was possible to predict the dose of APD needed to achieve normal values of ALP and HYPRO. In the 10 patients who achieved a normal ALP and 9 patients a normal HYPRO after more than 6 months treatment with APD (range 7-18 months), the predicted dose of APD agreed closely with the actual dose. In conclusion, our data support the idea that log dose APD/pretreatment BPS is a valid predictor of biochemical response in Paget's disease.

Alkaline Phosphatase↗
PubMed1992

A neuroendocrine cause of oncogenic osteomalacia.

All definite cases of oncogenic osteomalacia have, until now, been classified as mesenchymal tumours. We report here a case of oncogenic osteomalacia caused by a spinal tumour. Microscopically, it resembled the mixed connective tissue variant of previously described phosphaturic tumours. Immunohistochemical studies, however, showed the tumour cells to be positive for low molecular weight cytokeratin (CAM 5.2), S100 protein, PGP 9.5, and synaptophysin. Electron microscopy demonstrated neurosecretory granules. The histopathological findings strongly suggest that this is a neuroendocrine tumour.

Adult↗
PubMed1992

Comparison of low-dose intramuscular and intravenous salcatonin in the treatment of primary hyperparathyroidism.

The treatment of hypercalcaemia with low-dose salcatonin (100 U/d), administered either as a single intramuscular bolus or as a continuous intravenous infusion for five days, was examined in two groups of 10 patients with primary hyperparathyroidism, in a randomized open parallel study. Both the peak (0.31 +/- 0.035 mmol/L v 0.13 +/- 0.034 mmol/L) and overall (0.073 +/- 0.016 mmol/L v 0.018 +/- 0.016 mmol/L) hypocalcaemic responses were greater in the infusion group. The peak reduction in serum calcium occurred on day 2 of treatment after which there was a progressive attenuation of response. All the differences between the two methods of administration wer due to renal rather than bony effects of salcatonin. Possible causes of progressive resistance to treatment included reductions in sodium excretion and serum phosphate. It is concluded that low-dose salcatonin administered as a continuous infusion was more effective than the same dose given as a bolus. The kidney played a pivotal role both in the cause of the hypercalcaemia and in the response to treatment, including the rapid development of resistance which limits the use of salmon calcitonin in primary hyperparathyroidism to short-term reduction of serum calcium.

Alkaline Phosphatase↗
PubMed1990

Treatment of Paget's disease with intermittent low-dose infusions of disodium pamidronate (APD).

Disodium pamidronate (APD) is a potent inhibitor of bone resorption, with less risk of defective mineralization than earlier bisphosphonates. We assessed the response to six spaced low-dose intravenous infusions of APD given at intervals of approximately 6 weeks followed by weekly infusions if bone turnover remained abnormal. Three groups of 10 patients were studied, each group receiving infusions of 15, 30, or 45 mg. Hydroxyproline excretion fell by 62% and alkaline phosphatase was reduced by 72%, with no difference between the dose levels. A total of 21 patients (70%) achieved normal levels of bone turnover, indicating that low-dose infusions of APD are a safe and effective treatment for Paget's disease.

Alkaline Phosphatase↗
PubMed1990

Potentiation of calcitonin by corticosteroids during the treatment of the hypercalcaemia of malignancy.

Some patients treated for the hypercalcaemia of malignancy develop renal tubular resistance to the effects of calcitonin which is independent of concurrent changes in sodium excretion. This type of resistance can be overcome by the addition of corticosteroids. In other patients apparent renal resistance to calcitonin is a consequence of reduced sodium excretion and is unaffected by corticosteroids.

Aged↗
PubMed1990

Assessment of renal and skeletal components of hypercalcemia.

The management of hypercalcemia of malignancy is guided by assessments of its various components. Since the intestine usually makes no contribution to hypercalcemia under these circumstances, the problem is to measure the net efflux of calcium out of bone and the ability of the kidneys to excrete the unwanted calcium load. Established relationships between serum and urinary calcium excretion rates allow the quantitation of the relative contribution of an impaired glomerular filtration rate, of reduced renal tubular calcium reabsorption, and of increased bone resorption. Since the renal handling of calcium is closely related to that of sodium in the proximal nephron, the rate of sodium excretion is an important variable in these measurements. A practical approach to the separation of hypercalcemia into its renal and skeletal components is described in this article. Examples of how these measurements can be used to assess the responses to various types of therapy for malignancy-associated hypercalcemia are also given.

Bone and Bones↗
PubMed1990

Is vitamin D necessary for skeletal integrity in the elderly?

Serum 1.25 dihydroxyvitamin D concentrations were reduced in elderly patients with femoral neck fractures, irrespective of the presence of osteomalacia. This reduction was not attributable to a decrease in vitamin D binding protein. The low rate of bone turnover in these elderly patients might reduce the requirement for vitamin D and protect against the development of osteomalacia. Serum vitamin D metabolite concentration cannot be used as a screening test for osteomalacia in these patients.

Adult↗
PubMed1990

Advances in the management of Paget's disease of bone.

The advent of potent new bisphosphonates (diphosphonates) now makes it possible to restore and maintain normal bone turnover in many patients with Paget's disease of bone (osteitis deformans). This has necessitated a reappraisal of the indications for treatment, the ways in which disease activity and response are assessed, as well as the place of existing therapies. Measurements of urinary hydroxyproline and serum alkaline phosphatase remain the most useful markers of disease activity. Pyridinium crosslinks may prove to be more specific than hydroxyproline in the assessment of bone resorption but osteocalcin has been disappointing in monitoring the effect of treatment on bone formation. Etidronic acid (disodium etidronate), the first bisphosphonate introduced for clinical use, is a potent inhibitor of osteoclastic bone resorption but its potential is limited by the development of defective mineralisation with high dosage (10 to 20 mg/kg/day). The newer bisphosphonates, clodronic acid (clodronate) and pamidronic acid (pamidronate, APD), are free from this problem and appear able to control a wide range of disease activity. A small number of patients appear resistant to the agents but the underlying mechanism is unclear. The efficacy and safety of these bisphosphonates makes it likely that the threshold for treating asymptomatic patients will fall in the hope of preventing long term complications. These developments will lead to a reappraisal of the role of calcitonin which can now be administered by both the parenteral and intranasal routes. One focus of interest will be on the quality of the bone laid down during treatment. Meticulous radiographic studies have shown that calcitonin improves bone architecture and this may have particular relevance to the treatment of lytic disease. The relative merits of the different forms of therapy for Paget's disease need further evaluation, particularly with respect to the identification of specific advantages of individual drugs.

Humans↗
PubMed1990

Maintenance of serum calcium after total thyroparathyroidectomy.

We have studied calcium regulation in 11 consecutive patients undergoing radical surgery for upper aerodigestive tract malignancy. Eight patients received postoperative parenteral nutrition including calcium (19 mmol/day) and tri-iodothyronine (30 micrograms/day) supplementation. Three patients received enteral nutrition with calcium (70 mmol/day), 1.25 dihydroxycholecalciferol (1 microgram) and thyroxine (150 micrograms/day) via a nasogastric tube. Mean (SEM) corrected calcium fell from 2.42 (0.013) to 2.03 (0.036) mmol/l after 24 h (P less than 0.01). Replacement therapy generally maintained the serum calcium above 2.0 mmol/l. However, values were associated with only one episode of tetany. Phosphate increased from 1.10 (0.05) to 1.79 (0.11) mmol/l, 7-9 days postoperatively (P less than 0.001). Tubular calcium reabsorption fell and urinary calcium excretion rose, consistent with loss of parathyroid hormone (PTH) action on the distal nephron. However, the renal leak of calcium can be considerably reduced by concomitant salt depletion. This enhances proximal tubular sodium and calcium reabsorption thereby limiting calcium delivery to the distal nephron. This offsets the consequences of the loss of PTH which normally regulates distal calcium reabsorption.

Absorption↗
PubMed1989

Changes in osteocalcin after femoral neck fracture.

In a group of elderly patients with osteoporosis and femoral neck fracture, osteocalcin concentrations rose significantly in the first week after fracture fixation. The changes in osteocalcin correlated well with the changes in plasma 1,25-dihydroxycholecalciferol (P less than 0.001).

Aged↗
PubMed1988

Mechanisms of parathyroid hormone resistance in pseudohypoparathyroidism.

The problem with PHP is that it is almost certainly a heterogeneous condition encompassing a number of defects within the PTH receptor-adenylate cyclase complex. The clinical manifestations of PTH resistance are amplified and extended by a number of associated abnormalities. These include a low intracellular calcium concentration, secondary hyperparathyroidism, reduced production of 1,25-(OH)2D and perhaps the secretion of an abnormal PTH peptide. Almost every aspect of PTH function seems involved and this makes PHP a fascinating condition in which to test current views of the role of PTH in the integration of the calcium homoeostatic system.

Adenylyl Cyclases↗
PubMed1987

Biochemical response to combination of disodium etidronate with calcitonin in Paget's disease.

The biochemical responses to salmon calcitonin (SCT: 100 MRC units thrice weekly) and disodium etidronate (EHDP: 400 mg daily) alone and in combination for 6 months were compared in 72 patients with symptomatic Paget's disease of bone unresponsive to simple analgesic agents. SCT produced a 53% reduction in alkaline phosphatase (AP) and a 38% reduction in 24 h urinary hydroxyproline excretion (HYPRO). The response to EHDP was not significantly different--56% reduction in AP and 48% reduction in HYPRO. Their use in combination produced a significantly greater reduction of 71% in AP (P less than 0.002) and 69% reduction in HYPRO (P less than 0.0001). In those that remained symptomatic with increased disease activity treatment for longer than 6 months had a unpredictable effect and normal bone turnover was rarely achieved. Once therapy was withdrawn AP and HYPRO increased rapidly in those given SCT alone, returning to initial levels within 6 months. More sustained control of disease activity was achieved in those given EHDP either alone or with SCT but the combination retained the advantage obtained during treatment. Combinations of SCT + EHDP may find a place in the treatment of very active Paget's disease.

Alkaline Phosphatase↗
PubMed1987

Osteomalacia and femoral neck fractures in the elderly patient.

In a series of over 1000 elderly patients with femoral neck fracture, who were routinely screened by iliac crest bone biopsy, a 2% prevalence of osteomalacia was found. This low figure suggests that osteomalacia is not a significant predisposing factor in the development of these fractures and that routine screening is not cost-effective.

Aged↗
PubMed1987

Screening for osteomalacia in elderly patients with femoral neck fractures.

In this study 201 elderly patients with femoral neck fractures were compared with 30 osteomalacic patients with the same injury. Hypocalcaemia and a raised alkaline phosphatase level are common biochemical abnormalities in elderly patients with femoral neck fractures. In only a minority of patients, however, were they associated with histologically proven osteomalacia. By using the combination of hypocalcaemia and a raised alkaline phosphatase it is possible to identify a subgroup (approximately 10% of all admissions) in whom osteomalacia is relatively likely.

Aged↗