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)

The effect of alendronate on renal tubular reabsorption of phosphate.

We report the effects of alendronate on phosphate homeostasis in two patients. In a woman with postmenopausal osteoporosis, the infusion of alendronate (7.5 mg intravenously daily for 4 consecutive days) was not associated with secondary hyperparathyroidism despite a reduction in serum calcium. This was associated with a rise in serum phosphate and TmP/GFR. This response contrasted with those observed in 14 other patients with osteoporosis, in whom PTH rose significantly following the infusion of alendronate in association with a significant fall in serum phosphate and TmP/GFR. The second patient, a woman with Paget's disease, was treated with intravenous alendronate (10 mg daily for 5 consecutive days) on two occasions for relapse of disease activity. On the first occasion there was a 150% rise in serum PTH associated with a fall in serum phosphate and TmP/GFR. On the second occasion, when the rise in serum PTH was less marked, there was a rise in serum phosphate and TmP/GFR. We conclude that alendronate may increase renal tubular reabsorption of phosphate, but that this effect is usually offset by secondary hyperparathyroidism.

Effects of five daily 1 h infusions of alendronate in Paget's disease of bone.

We report a randomized placebo-controlled double-blind study of amino-hydroxybutylidene bisphosphonate (alendronate), infused over 1 h, in 15 patients with Paget's disease of bone. Alendronate, 10 mg/day for 5 days, suppressed urinary hydroxyproline to 44.9 +/- 4.8% and serum alkaline phosphatase to 74.6 +/- 5.4% of their pretreatment values within 1 month of the start of treatment. Within 5 months of the start of treatment serum alkaline phosphatase fell to 47.9 +/- 6.3% of pretreatment values. These effects were associated with a decrease in serum calcium and phosphate and in urinary calcium excretion and with a rise in serum iPTH values. A transient fever was observed in 3 of 10 patients who received alendronate during the course of the infusions, and this was associated with a decrease in the total and differential white cell count. No adverse effects were noted on renal function as judged by glomerular filtration rate and indices of proximal and distal tubular function. This regimen may simplify the management of patients with Paget's disease of bone.

Radiographic changes in algodystrophy of the hand.

It is not certain to what extent the radiographic features of post-traumatic algodystrophy can be differentiated from disuse atrophy following trauma. A semi-quantitative scoring system has been devised, grading the dominant features seen on radiography in both conditions following Colles' fracture. The technique had intra- and inter-observer errors of 14% and 17% respectively. When applied prospectively 7 weeks after Colles' fractures, there was a significantly greater score in patients with algodystrophy (p less than 0.001) than those without. Analysis of the scores was performed to identify a score for the optimal identification of algodystrophy. At a score of four or greater, 87.5% of patients with algodystrophy were positively identified with a positive predictive value of 83%. It is suggested that use of this scoring system will aid in the early diagnosis of algodystrophy.

Effects of amino-butylidene diphosphonate in hypercalcemia due to malignancy.

We studied the effect of a single 5 mg intravenous infusion of amino-butylidene diphosphonate (ABDP) in nine patients with hypercalcemia of malignancy, in whom serum calcium values were stable or rising after intravascular volume expansion. Serum calcium fell progressively in all patients and in seven reached the normal reference range by day 6 (p less than 0.001). The decrease in serum calcium was associated with a decrease in the fasting urinary calcium/creatinine ratio (p less than 0.05). Hypercalcemia recurred in seven of the patients by day 12, but two patients remained normocalcemic for 21 days. We conclude that ABDP is a highly potent diphosphonate and that a single intravenous infusion is capable of inhibiting tumour-mediated bone resorption for several days.

The management of the painful first metatarsophalangeal joint in the older patient. Arthrodesis or Keller's arthroplasty?

We report a prospective randomised trial comparing Keller's arthroplasty and arthrodesis of the first metatarsophalangeal joint for the management of symptomatic hallux valgus and hallux rigidus in the older patient. In 81 patients (110 feet), with a minimum of two years follow-up, both procedures gave a similar degree of patient satisfaction and symptom relief. The incidence of metatarsalgia was also similar. As there were no obvious advantages to arthrodesis, and since six out of 50 arthrodesed toes required revision, we suggest that Keller's arthroplasty is the better operation in these patients.

Treatment of Paget's disease of bone with aminohydroxybutylidene bisphosphonate.

This study examined the effects of aminohydroxybutylidene bisphosphonate in 30 patients with Paget's disease of bone, administered as an intravenous infusion for 5 consecutive days. Treatment (5 mg IV daily) induced marked suppression of biochemical indices of disease activity. Urinary excretion of hydroxyproline fell to 50% of pretreatment values within 2 weeks and was followed by a similar, but later, decline in the serum activity of alkaline phosphatase. Disease activity remained suppressed throughout the 6 months of observation, and only 1 patients showed biochemical signs of an early relapse. Symptomatic improvement was noted in 27 of the 30 patients. Bone biopsies, undertaken in 10 patients, indicated no adverse effects on mineralization. Transient falls were noted in the total white cell count, particularly the lymphocyte and neutrophil fractions, and were associated with short-lived fever in 3 patients. We conclude that short courses of intravenous AHButBP provide a promising treatment for active Paget's disease of bone.

A comparison of the acute effects of subcutaneous and intranasal calcitonin.

1. We studied the acute effects of intranasal and subcutaneous calcitonin in 40 patients with active Paget's disease of bone. Patients received a single dose of either 400 units of calcitonin delivered as a nasal spray, or 1, 10 or 100 units of subcutaneous calcitonin, or placebo. 2. Subcutaneous salmon calcitonin, administered at doses of 1, 10 and 100 units to nine patients with Paget's disease of bone, induced a dose-dependent fall in the serum calcium. This calcium-lowering effect was not seen with a second group of nine patients receiving placebo. 3. The lower doses of calcitonin had significant effects, and these were more pronounced in patients with lower rates of bone turnover. 4. Four hundred units of calcitonin administered as a nasal spray induced effects qualitatively similar to those seen with subcutaneous calcitonin, with an efficacy equivalent to approximately 30 units of subcutaneous calcitonin. 5. We conclude that the bioequivalence of calcitonin given by intranasal insufflation is low compared with its parenteral administration. The intranasal route may be more appropriate for managing patients with disorders associated with low bone turnover.

Broadband ultrasound attenuation in the os calcis: relationship to bone mineral at other skeletal sites.

1. We have examined the relationship between broadband ultrasound attenuation in the os calcis and measurements of bone mineral in the distal forearm and lumbar spine of normal and postmenopausal osteoporotic women. 2. Values of broadband ultrasound attenuation in postmenopausal women with vertebral osteoporotic fractures were significantly lower (35%) than in normal pre- and peri-menopausal women (55.4 +/- 3.8 and 79.6 +/- 0.8 dB/MHz, respectively). 3. Broadband ultrasound attenuation correlated significantly with bone mineral content measured in the distal forearm by single-photon absorptiometry (r = 0.77, P less than 0.0001) and with bone mineral content (r = 0.66, P less than 0.0001) and bone mineral density (r = 0.72, P less than 0.0001) measured in the lumbar spine by dual-photon absorptiometry. 4. Although significant, these correlations are not sufficiently close to be predictive. However, the accuracy of broadband ultrasound attenuation in discriminating between normal subjects and patients with vertebral fracture compared very favourably with direct measurements in the spine by dual-photon absorptiometry. 5. Broadband ultrasound attenuation, but not the other measurements, correlated significantly with age in the osteoporotic patients (r = 0.50, P less than 0.05). 6. These findings may reflect the partial dependence of broadband ultrasound attenuation on the intrinsic trabecular architecture of cancellous bone, the disruption of which contributes to an increase in fracture risk.

Improvement in the deformity of the face in Paget's disease treated with diphosphonates.

We studied nine patients with Paget's disease affecting the skull or facial bones, who were subsequently treated with either dichloromethylene diphosphonate (clodronate) or ethylene-1-hydroxy-1,1-diphosphonate (etidronate). Long-term treatment induced a clinical and biochemical improvement in eight, and this was associated with a reduction in maxillary or skull volume as assessed by quantitative stereophotogrammetry. The one patient whose disease was resistant to treatment with diphosphonate, showed no change in maxillary shape. These studies suggest that the long-term control of disease activity attained with diphosphonates, results in the improvement of skeletal deformity.

Preoperative lower limb venography in patients undergoing total hip arthroplasty.

Using bilateral ascending venography, the authors examined 93 consecutive patients undergoing total hip arthroplasty for the presence of asymptomatic preoperative leg vein thrombosis. Radiologic abnormalities were seen in only four patients, and this was not statistically significant (P greater than .1). There were no complications from the procedure. It is suggested that routine preoperative screening for deep vein thrombosis prior to hip arthroplasty is unnecessary but may be appropriate in patients at particularly high risk for thromboembolic complications.

Surgical complications of amyloid disease.

The case of a man with primary systemic amyloidosis without myelomatosis and long-term survival is described. The patient has had major surgical complications from large amyloid deposits in the colon, dorsal spine and peritoneal cavity. The patient remains well 14 years after diagnosis.

Rupture of the stomach after hemorrhage from a gastric ulcer.

A case of nontraumatic gastric rupture in an adult is reported. Rupture occurred after distention of the stomach with blood from a bleeding gastric ulcer.

Endoscopic sphincterotomy for retained common bile duct stones in patients with T-tube in situ in the early postoperative period.

We report on thirty-nine patients who underwent endoscopic sphincterotomy (ES) and stone extraction for retained common bile duct calculi with a T-tube in situ. Sixteen of the patients had undergone unsuccessful attempts at removal by flushing or dissolution by cholesterol solvents. A total of 76 stones were present: 53 distal to the T-tube and 23 proximal to the T-tube. ES and clearance of the common bile duct was achieved in 37 patients (95 per cent) and complications occurred in three patients (7.7 per cent). This method is an effective and relatively safe method in the early postoperative period allowing rapid treatment during the same admission as for the original operation and early hospital discharge.