The safety of osteoporosis medication.

Osteoporosis is a common, costly and serious disease, which is still too often regarded as an inevitable part of the normal ageing process and therefore sub-optimally treated, especially in the elderly--in fact, only two out of every 10 patients who sustain a hip fracture receive any form of assessment or prophylactic therapy for osteoporosis. One out of five patients die within 1 year after a hip fracture, and < 50% are capable of leading an independent life. Yet very effective anti-fracture therapy, capable of reducing fracture risk by 35 - 60%, is available. A number of publications have recently questioned the safety of drugs routinely used to treat patients with osteoporosis. This paper attempts to put the situation into perspective and expresses the National Osteoporosis Foundation of South Africa's view on the safety of these drugs. Their efficacy in preventing skeletal fractures and their cost-effectiveness are not addressed in any detail. The paper emphasises the fact that all osteoporosis medications have side-effects, some of which are potentially life-threatening.

Upper gastrointestinal and overall tolerability of alendronate once weekly in patients with osteoporosis: results of a randomized, double-blind, placebo-controlled study.

OBJECTIVE: To compare the upper gastrointestinal (GI) and overall tolerability profiles of alendronate 70 mg once weekly with placebo. RESEARCH DESIGN AND METHODS: This 12-week international, multi-center, randomized, double-blind, placebo-controlled trial included 449 postmenopausal women and men with osteoporosis at 44 sites in 19 countries in Europe, the Americas, Africa, and Asia-Pacific. Subjects were randomized to alendronate 70 mg once weekly or matching placebo in a 1:1 ratio. MAIN OUTCOME MEASURES: The safety and tolerability of weekly alendronate and placebo were captured as clinical and laboratory adverse events. The primary endpoint was upper GI tolerability based on the incidence of upper GI tract adverse events. Secondary endpoints included the percentage of subjects who discontinued therapy due to a drug-related upper GI adverse event. Change from baseline in bone turnover as measured by the urinary N-telopeptide-collagen crosslinks corrected for creatinine (NTx/Cr) was assessed at 12 weeks as an indicator of efficacy. RESULTS: The percentages of subjects reporting an upper GI tract adverse event in the alendronate 70 mg once weekly group (9.8%) and the placebo group (9.4%) were similar. The risk difference between the two treatment groups (alendronate minus placebo) was 0.4% [95% confidence interval (CI), -5.1%, 5.9%]. Percentages of subjects who discontinued due to a drug-related upper GI adverse event were also similar (alendronate 2.7%; placebo 2.2%; risk difference 0.4%, 95% CI, -2.4, 3.3). The overall tolerability profile of alendronate 70 mg once weekly, as measured by the percentage 8.0% (95% CI, 1.4%, 15.0%) increase in the of subjects reporting any adverse event, was similar to that of placebo (risk difference 2.1%, 95% CI -6.9, 11.0). There was a significant 43.3% (95% CI, -47.9%, -38.3%) decrease from baseline in urinary NTx/Cr in the alendronate group compared with an placebo group at Week 12. CONCLUSION: Alendronate 70 mg administered once weekly to women and men with osteoporosis has an upper GI and overall tolerability profile similar to that of placebo.

Modeling of subcutaneous absorption kinetics of infusion solutions in the elderly using technetium.

Absorption kinetics of solutes given with the subcutaneous administration of fluids is ill-defined. The gamma emitter, technitium pertechnetate, enabled estimates of absorption rate to be estimated independently using two approaches. In the first approach, the counts remaining at the site were estimated by imaging above the subcutaneous administration site, whereas in the second approach, the plasma technetium concentration-time profiles were monitored up to 8 hr after technetium administration. Boluses of technetium pertechnetate were given both intravenously and subcutaneously on separate occasions with a multiple dosing regimen using three doses on each occasion. The disposition of technetium after i.v. administration was best described by biexponential kinetics with a Vss of 0.30 +/- 0.11 L/kg and a clearance of 30.0 +/- 13.1 ml/min. The subcutaneous absorption kinetics was best described as a single exponential process with a half-life of 18.16 +/- 3.97 min by image analysis and a half-life of 11.58 +/- 2.48 min using plasma technetium time data. The bioavailability of technetium by the subcutaneous route was estimated to be 0.96 +/- 0.12. The absorption half-life showed no consistent change with the duration of the subcutaneous infusion. The amount remaining at the absorption site with time was similar when analyzed using image analysis, and plasma concentrations assuming multiexponential disposition kinetics and a first-order absorption process. Profiles of fraction remaining at the absorption site generated by deconvolution analysis, image analysis, and assumption of a constant first-order absorption process were similar. Slowing of absorption from the subcutaneous administration site is apparent after the last bolus dose in three of the subjects and can be associated with the stopping of the infusion. In a fourth subject, the retention of technetium at the subcutaneous site is more consistent with accumulation of technetium near the absorption site as a result of systemic recirculation.

Testicular scintigraphic findings two to three months after torsion. Correlation with sonography and histopathology.

A patient with a nontender testicular mass had sonographic abnormalities compatible with but not entirely typical of a chronic torsion. His scintigraphic studies, done on the same day as ultrasonography and 1 month later, revealed only findings consistent with a very mild subsiding scrotal inflammatory process. On surgical exploration and pathologic examination, it was found that he had an organizing infarct of the testicle secondary to torsion. The clinical history, diagnostic studies, and microscopic slides of the surgical specimen were reviewed. It appeared that tissue granulation and lipogranulomatous changes in the epididymis, known histologic sequelae to the unusually prolonged testicular torsion of 2-3 months, produced scintigraphic findings different from those which have been described for a late or an atrophic torsion.

Subcutaneous fluid administration in elderly subjects: validation of an under-used technique.

In a crossover study in six volunteers over the age of 65, absorption of 500 mL of normal saline given subcutaneously was compared with that given intravenously. Tritiated water and technetium pertechnetate were used as water tracers. Tritium radioisotope levels in the blood increased in a smooth curve during subcutaneous infusion, reaching equilibrium levels within 60 minutes. The area under the curve after subcutaneous infusion was almost identical to that after intravenous infusion in all subjects. Radioactivity could not be demonstrated at the subcutaneous site 1 hour after completion of the infusion. Subcutaneous infusion is an effective method of giving fluid to elderly people and deserves more widespread use.

Detection of renal calculi: the value of tomography.

Two hundred patients were evaluated to determine the sensitivity of tomography in detecting calculous disease of the upper urinary tract. In all cases, patients had routine scout radiographs of the abdomen and five precontrast tomograms of the kidneys. Of the 200 patients, 28 (14%) had renal calculi. Of these, 11 (39%) had either unsuspected or more calculi detected on tomography than seen on abdominal radiographs. Patients with symptoms suggestive of calculous disease should be evaluated with tomography in addition to plain films in order to optimize the detection and the extent of calculous disease involving the urinary tract.

Diagnosis of acromegaly on cranial computed tomography.

The characteristic features of acromegaly as demonstrated on cranial computed tomography (CT) are described. These features relate to the increased soft tissue bulk and overpneumatization of sinuses and air cells, as well as the generalized bony overgrowth associated with high growth hormone (GH) levels. In the assessment of these features, the computer window settings must be adjusted accordingly for separate visualization of soft tissues, calvarial bones and cerebral tissue on the scan images. We found positive features in CT scans of 13 patients with established acromegaly and were able to suggest the diagnosis prospectively in 2 additional cases. The finding of an enlarged pituitary fossa should lead the radiologist to search carefully for the ancillary signs of acromegaly on the scans, thus confirming the diagnosis. When an enlarged sella turcica or an enhancing intrasellar mass is not demonstrated, the recognition of the other features on cranial CT scans may be important in suggesting the diagnosis of acromegaly to the clinician.

Blood-brain and blood-lung barrier alteration by dysbaric exposure.

Failure of certain circulating substances to penetrate specific organs led to the concept of blood-organ barriers. Such barriers can be altered by various physical or chemical means. This report concerns modification of the blood-brain barrier (BBB) and blood-lung barrier (BLB) by dysbaric exposure. Trypan blue was intravenously administered to 19 experimental rabbits (subjected to compression-decompression) and to 11 controls (kept at ambient pressure). Gross and microscopic examination and measurements of dye extracted from tissues revealed greater dye penetration into lung and brain of the experimental animals. Dye concentration in brain was 12.10 microgram/g tissue in experimental and 2.93 microgram in control animals; in lungs it was 935 microgram and 434 microgram, respectively (0.01 greater than P 0.001). Increased permeability of BBB and BLB was associated with intravascular bubbles. The mechanism of BBB and BLB alteration may involve chemical agents activated by gas-blood interface or vascular injury produced by bubbles. These observations could have pathogenetic implications in decompression sickness and may suggest new methods for facilitating penetration of therapeutic agents into the brain.

Protein calorie malnutrition and nutritional anaemia in Black pre-school children in a South African semirural community.

The incidence of nutritional anaemia and of protein calorie malnutrition in 119 randomly selected Black children living in the Muldersdrift area was studied. The ecology of nutritional problems in the community was also investigated. Major problems in the area were poor educational and medical facilities, a high childhood mortality rate and poor cash incomes. An important factor which influenced nutrition was large family size. The incidence of protein calorie malnutrition was 27,6% and of nutritional anaemia 13,3%. In the second year of life the incidence of anaemia was 27,3%. The main cause of anaemia was iron deficiency.