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Biomedical subjects

J A Kanis

Publications and source records attributed to J A Kanis.

At least 19 recordsLinked to original sources
PubMed1995

Treatment of osteoporosis in elderly women.

Prevention of osteoporosis is better than cure. This intuitive wisdom is strengthened by knowledge that osteoporosis due to gonadal deficiency is associated with a disruption of skeletal architecture that is irreversible by current treatments. Moreover, it is commonly assumed that bone is lost more slowly in later life than in the several years after the menopause, so that factors other than decreasing bone mass are assumed to be of greater importance for fracture risk. With the exception of fluoride, current treatments have not been shown to restore skeletal mass in patients with osteoporosis. These views have suggested that the management of osteoporosis in the elderly is of limited value and have reinforced the importance of preventive measures. Notwithstanding, there are several reasons for believing that intervention late in the natural history of bone loss is worthwhile. Whereas cross-sectional studies suggest that bone loss declines in later years, prospective studies indicate that bone loss is progressive and indeed accelerates in extreme old age. Moreover, the measurement of bone mass predicts future fracture in the elderly as effectively as it does at the time of the menopause. There are also several reasons why preventive approaches at the time of the menopause have limited applicability. Since current preventive treatments cannot be given indefinitely, a crucial question concerns the extent to which reversal of effect occurs after treatment withdrawal. If catch-up bone loss does occur, it decreases markedly the cost-effectiveness of therapeutic intervention at the menopause and provides a convincing rationale for the use of interventions at a much later age. The optimum age for starting treatment is not yet determined but might be best directed 15 or so years after the menopause, well before the mean age of hip fracture. Since hip fracture provides the greatest socioeconomic impact of osteoporosis and since evidence is accumulating that treatments favorably affect hip fracture risk, it is suggested that greater attention should be given to the management of osteoporosis in the elderly.

Age Distribution↗
PubMed1995

Effect of alfacalcidol on natural course of renal bone disease in mild to moderate renal failure.

OBJECTIVE: To determine whether alfacalcidol--used in management of overt renal bone disease--may safely prevent renal bone disease when used earlier in course of renal failure. DESIGN: Double blind, prospective, randomised, placebo controlled study. SETTING: 17 nephrology centres from Belgium, France, the Netherlands, and the United Kingdom. SUBJECTS: 176 patients aged 18-81 with mild to moderate chronic renal failure (creatinine clearance 15-50 ml/min) and with no clinical, biochemical, or radiographic evidence of bone disease. INTERVENTIONS: Alfacalcidol 0.25 micrograms (titrated according to serum calcium concentration) or placebo given for two years. MAIN OUTCOME MEASURES: Quantitative histology of bone to assess efficacy of treatment and renal function to assess safety. RESULTS: 132 patients had histological evidence of bone disease at start of study. Biochemical, radiographic, and histological indices of bone metabolism were similar for the 89 patients given alfacalcidol and the 87 controls given placebo. After treatment, mean serum alkaline phosphatase activity and intact parathyroid hormone concentration had increased by 13% and 126% respectively in controls but had not changed in patients given alfacalcidol (P < 0.001). Hypercalcaemic episodes occurred in 10 patients given alfacalcidol (but responded to decreases in drug dose) and in three controls. Histological indices of bone turnover significantly improved in patients given alfacalcidol and significantly deteriorated in controls: among patients with abnormal bone histology before treatment, bone disease resolved in 23 (42%) of those given alfacalcidol compared with two (4%) of the controls (P < 0.001). There was no difference in rate of progression of renal failure between the two groups. CONCLUSION: Early administration of alfacalcidol can safely and beneficially alter the natural course of renal bone disease in patients with mild to moderate renal failure.

Adolescent↗
PubMed1995

The effects of intravenous alendronate in Paget's disease of bone.

We studied the effects of intravenous alendronate on disease activity in 36 patients with active Paget's disease of bone. Alendronate was administered to 3 groups of 12 patients at doses of 2.5, 5, and 10 mg intravenously daily for 5 consecutive days. The patients were matched for disease activity. Symptomatic improvement was seen in at least 10 patients in each treatment group. Alendronate induced a dose-dependent suppression of biochemical indices of bone turnover in all patients. A significant reduction in the mean fasting urinary excretion of hydroxyproline occurred within 2 days of starting treatment, reaching a nadir at 2-4 weeks, which was most marked in patients receiving 10 mg of alendronate (p < 0.05). There was a slower fall in serum alkaline phosphatase activity with maximal suppression occurring 3 months after the start of treatment. The degree of suppression was least for those receiving 2.5 mg of alendronate (p < 0.05) but no difference in response was observed for the other dosages. The duration of response was also dose-related. A significant fall in the serum calcium and urinary excretion of calcium occurred from the second day of treatment but returned to pretreatment values by 4 months. A transient fall in the mean lymphocyte count was observed, which was similar for each group. This was associated with a short-lived fever in 3 patients receiving 10 mg, in 4 patients receiving 5 mg, and in 2 patients receiving 2.5 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Acute effects of deflazacort and prednisone on rates of mineralization and bone formation.

The aims of this study were to determine (1) whether acute suppression of bone formation could be evaluated after the administration of corticosteroids in man by quantitative bone histomorphometry; and (2) whether there were significant differences between the effects of prednisone and its analog deflazacort. Thirteen patients who needed high-dose corticosteroid therapy were randomly allocated to two groups of treatment (prednisone or deflazacort). Quantitative bone histomorphometry, using the technique of triple labeling, and biochemical measurements of bone turnover were studied. There were no differences in biochemical indices of bone turnover between prednisone and deflazacort at the beginning and end of the 15 days of treatment course. During corticosteroid treatment, there were no significant changes in biochemical indices of bone turnover but a significant decline in total alkaline phosphatase (P < 0.01). Histomorphometric indices, as revealed by measurements of tetracycline interval and extent of labeling, showed no significant differences in either mineral apposition rate or bone formation rate in the two groups. We conclude that the acute glucocorticoid suppression of bone turnover by glucocorticoids is not detectable within the first 2 weeks of treatment by histomorphometric techniques. No differences in bone effects of prednisone and deflazacort were detected in this short-term study.

Adult↗
PubMed1995

Rationale for the use of alendronate in osteoporosis.

Bisphosphonates are being used in disorders associated with accelerated resorption of bone, particularly Paget's disease of bone and the bone disease of malignancy. Their undoubted biological efficacy and relatively low apparent toxicity make them attractive candidates for the management of osteoporosis. The bisphosphonate alendronate has many characteristics which suggest that it is suitable for use in osteoporosis. It is a potent inhibitor of osteoclast-mediated bone resorption with no adverse effect on the mineralization of bone. Earlier studies have shown it to be one of the most active bisphosphonates in Paget's disease and the hypercalcemia of malignancy. In common with other bisphosphonates tested thus far, alendronate appears to inhibit bone loss in a variety of experimental models of osteoporosis. Long-term studies are needed to determine its steady-state effects on bone mass in man. Most data indicate that alendronate is capable at least of decreasing the rate of bone loss, and might even induce increments in bone mass for many years. Since the experimental studies show that the increase in bone mass observed with alendronate is associated with an increase in bone strength, its use is likely to decrease the frequency of fractures. However, direct clinical evidence for this requires the outcome of well-designed long-term prospective studies.

Alendronate↗
PubMed1995

A randomised double-blind comparison of intravenous pamidronate and clodronate in the hypercalcaemia of malignancy.

In conjunction with rehydration, the bisphosphonates are the treatment of choice for hypercalcaemia of malignancy. Single infusions of either pamidronate or clodronate are usually effective, but a direct comparison of the two agents given at the highest doses commonly used has not been performed. Forty-one patients (15 breast, 12 squamous carcinomas, four lymphomas, four bladder, two prostate and four others) with hypercalcaemia of malignancy (corrected serum calcium > 2.7 mmol l-1) persisting after 48 h of saline rehydration were randomly allocated to receive a 4 h intravenous (i.v.) infusion of either pamidronate 90 mg or clodronate 1500 mg. No other systemic anti-cancer treatment was prescribed. There were no significant differences in the post-hydration serum calcium values (mean 3.17 mmol l-1 for pamidronate and 3.06 mmol l-1 for clodronate), tumour type or frequency of bone metastases between the two treatments. One patient on each treatment died within 2 days and was not assessable for response. A total of 19/19 (100%) patients achieved normocalcaemia following pamidronate and 16/20 (80%) with clodronate. The median time to achieve normocalcaemia was 4 days (range 2-14) for pamidronate and 3 days (range 2-6) with clodronate. The median duration of normocalcaemia was 28 days (range 10-28+ days) after pamidronate and 14 days after clodronate (range 7-21 days) (P < 0.01). Two patients who failed to respond to clodronate were successfully treated with pamidronate and achieved normocalcaemia for 14 and > 28 days respectively. Two patients experienced fever after pamidronate but no significant toxicity was observed with either treatment. We conclude that both agents are effective in the management of hypercalcaemia of malignancy. At the doses studied, the effects of pamidronate are more complete and longer lasting than those of clodronate.

Bone Neoplasms↗
PubMed1995

Double-blind, placebo-controlled, dose-response trial of oral clodronate in patients with bone metastases.

PURPOSE: Despite evidence that clodronate inhibits tumor-induced osteolysis, no studies have directly assessed the optimal dose for long-term treatment. The aim of this double-blind, placebo-controlled study was to determine the safety and efficacy of different doses of clodronate in affected patients. PATIENTS AND METHODS: Eighty-four patients with tumor-induced osteolysis were randomized to receive treatment with placebo, or 400 mg, 1,600 mg, or 3,200 mg of clodronate, daily for 4 weeks. Patients were reviewed weekly during treatment. Fasting urinary calcium excretion was the primary variable used to assess response. Visual analog pain scores and adverse events were documented. RESULTS: In the clodronate-treated groups, there was a dose-dependent reduction in fasting calcium excretion with a highly significant difference between placebo and 1,600 mg clodronate (P = .0002) and placebo and 3,200 mg clodronate (P = .0001), but no significant difference between 1,600 mg and 3,200 mg clodronate. There was no discernible change in pain scores or analgesic requirements. Bone-derived isoenzyme alkaline phosphatase values increased in all groups, with a significant difference between baseline and final values in the 1,600-mg and 3,200-mg groups (P < .01 and P = .03, respectively). Adverse events were distributed evenly across the four treatment groups. Compliance was greater than 99% in all treatment groups. CONCLUSION: Oral clodronate at a dose of 1,600 mg or 3,200 mg will inhibit bone resorption. Since there was no significant difference between these two doses in terms of efficacy at 4 weeks, 1,600 mg/d can be recommended for long-term treatment. This dose is well tolerated and may promote bone repair, as judged by increases in bone alkaline phosphatase levels.

Administration, Oral↗
PubMed1995

Cost-effectiveness of preventing hip fractures in the elderly population using vitamin D and calcium.

Recent evidence suggests that vitamin D and calcium can reduce the incidence of hip fracture amongst elderly women. We estimated the costs of using either parenteral vitamin D alone, or oral vitamin D plus calcium, in a number of treatment strategies. These were: all women in a community setting; women with low body mass index (BMI) in the community; women in nursing homes; women with low BMI in nursing homes. The cost per averted fracture amongst women living in the community through the use of parenteral vitamin D alone was 946 pounds, and the cost per averted hip fracture was 2317 pounds. Inclusion of calcium significantly increased the cost to 14, 240 pounds for any fracture and 22, 379 pounds for hip fractures. However, targeting either treatment on women with the lowest BMI reduced the cost of averting a hip fracture, as did targeting women living in nursing homes. After removing cost savings from treatment costs, savings to the NHS occurred for all parenteral vitamin D strategies but only one of the oral vitamin D and calcium strategies. Preventing fractures with injectable vitamin D is likely to produce savings for the NHS. The addition of calcium will increase costs significantly unless the intervention is targeted on those at high risk.

Administration, Oral↗
PubMed1995

Bone loss after tibial fracture. Evaluated by dual-energy X-ray absorptiometry.

We evaluated changes in bone mineral density (BMD) after tibial fractures, both at the site of fracture and at adjacent sites, using dual-energy X-ray absorptiometry. Five patients were studied prospectively for six months after fractures of the midshaft treated by intramedullary nailing or the application of an external fixator. We also reviewed 21 adult and 10 children who had sustained fractures of the tibia at least five years previously, comparing BMD in the injured limb with that in the non-injured limb and in a control group of 10 normal subjects. We found a significant fall in BMD distal to a tibial fracture; this was evident at one month, fell to approximately 50% of normal at three months and persisted at six months. We found no significant improvement with weight-bearing. Review at 5 to 11 years after adult midshaft fractures showed persistent bone loss in the distal tibia (46.5 +/- 9.8% of control values), but persisting sclerosis at old fracture sites (172 +/- 38% of control values). In contrast, we found no significant differences in BMD between the injured and control limb after fractures sustained in childhood either at the fracture site or in the distal segment. We conclude that, in adults, tibial fractures are associated with definite and persistent post-traumatic loss of distal BMD.

Absorptiometry, Photon↗
PubMed1994

Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group.

The criteria required for an effective screening strategy for osteoporosis are largely met in Caucasian women. The disease is common and readily diagnosed by the measurement of bone mineral with single- or dual-energy absorptiometry. Such measurements have high specificity but lower sensitivity, so that the value of the technique is greater for those identified as being at higher risk. Against this background there is little evidence that osteoporosis can usefully be tackled by a public health policy to influence risk factors such as smoking, exercise and nutrition. This suggests that it is appropriate to consider targetting of treatment with agents affecting bone metabolism to susceptible individuals. Since the main benefits of the use of hormone replacement therapy (HRT) are probably on cardiovascular morbidity, the major role for selective screening is to direct non-HRT interventions. An appropriate time to consider screening and intervention is at the menopause, but screening at later ages is also worthy of consideration. Since the cost of screening is low and that of bone-active drugs is high, the selective use of screening techniques will improve the cost-benefit ratio of intervention.

Adult↗