Regional patterns of bone loss and altered bone remodeling in response to calcium deprivation in laboratory rabbits

Summary This study explores the effects of a calcium-deficient diet on patterns of bone remodeling, and examines regional differences in the amount of bone lost. Skeletally mature female rabbits (n=6) were fed a calcium-deficient diet (0.10% Ca²⁺ and 0.50% P) for 14 weeks. A separate group of rabbits (n=4) were fed a maintenance diet (1.2% Ca²⁺ and 0.45% P). Bone mineral content, serum calcium, and serum phosphorus were measured each week during the experimental period. Following sacrifice, the L₃ vetebra, femoral head, proximal tibial metaphysis, and tibial midshaft were analyzed histomorphometrically. Rabbits had 20% less vertebral bone after only 14 weeks of a calcium-deficient diet. As in human postmenopausal osteoporosis, bone loss in calcium-deficient rabbits occurs in the trabecular bone of the lumbar spine before that in the trabecular bone of the lower extremity. Calcium-deficient diets alone do not lead to increased osteoid volume or thickness. Because bone loss is relatively rapid and because the pattern of loss is similar in some respects to that found in humans, adult rabbits may provide an attractive model of calcium deficiency osteoporosis in a skeletally mature mammal in which remodeling is predominant over modeling.     

Risk factors for rhabdomyolysis with simvastatin and atorvastatin.

OBJECTIVE: To assess the frequency of risk factors for rhabdomyolysis with simvastatin and atorvastatin in cases reported to the Australian Adverse Drug Reactions Advisory Committee (ADRAC). DESIGN: Reports meeting the definition of rhabdomyolysis were reviewed for risk factors including age > or = 70 years, dose > or = 40 mg, hepatic dysfunction, diabetes mellitus, hyperkalaemia, hypothyroidism and the use of concomitant interacting medications. RESULTS: Only one report associated with simvastatin and five reports associated with atorvastatin did not list any risk factors for rhabdomyolysis. Interacting medicines featured in 77% of reports of rhabdomyolysis associated with simvastatin and 44% of reports associated with atorvastatin. A comparison of the age profile for reports of atorvastatin- and simvastatin-associated rhabdomyolysis with that for all adverse drug reaction reports received, and for all reports of muscle disorders, suggested a trend towards an increasing risk of rhabdomyolysis with increasing age with simvastatin but not with atorvastatin. Similarly, comparing prescribed tablet strengths from Pharmaceutical Benefits Scheme data with the HMG-CoA reductase inhibitor ('statin') doses in reports of rhabdomyolysis suggested a dose-related risk with simvastatin, but a less increased risk with high-dose atorvastatin. CONCLUSION: Risk factors for rhabdomyolysis featured in nearly all of the reports of statin-associated rhabdomyolysis and the majority of reports listed multiple risk factors, although dependence on risk factors appeared to be stronger with simvastatin than atorvastatin. The multiplication of risk factors in patients taking simvastatin and atorvastatin should be minimised.     

Experimental stress fractures of the tibia. Biological and mechanical aetiology in rabbits

We have shown that stress fractures can be induced in the tibial diaphysis of an animal model by the repeated application of non-traumatic impulsive loads. The right hind limbs of 31 rabbits were loaded for three to nine weeks and changes in the bone were monitored by radiography and bone scintigraphy. The presence of stress fractures was confirmed histologically in some cases. Most animals sustained a stress fracture within six weeks and there was a positive correspondence between scintigraphic change and radiological evidence. Microscopic damage was evident at the sites of positive bone scans. The progression, location, and time of onset of stress fractures in this animal model were similar to those in clinical reports, making the model a useful one for the study of the aetiology of stress fractures.     

Evaluation of non-invasive blood pressure measurement by the Finapres method at rest and during dynamic exercise in subjects with cardiovascular insufficiency

The accuracy and precision of the Finapres in recording rest and exercise blood pressure compared with the intra-arterial (aortic and brachial) and random-zero sphygmomanometer methods was assessed in 84 ischaemic patients in three different studies. Firstly, comparison at rest with the aortic intraarterial pressure in 50 ischaemic patients demonstrated that the Finapres systolic (136.5 ± 21.1 vs. 129.3 ± 19.0 mmHg;p < 0.001) and mean (92.4 ± 13.4 vs. 90.7 ± 11.4 mmHg;p < 0.001) arterial pressures were higher and diastolic pressures lower (70.4 ± 11.5 vs. 71.5 ± 9.8 mmHg;p < 0.001). The reproducibility of the Finapres and invasive method was similar for systolic (4.6% vs. 4.0%), diastolic (2.8% vs. 2.7%) and mean (3.3% vs. 3.0%) blood pressures. Second, in seven subjects studied twice at rest and during 4 min supine bicycle exercise, the exercise increase in blood pressure was greater on the Finapres compared with the brachial intra-arterial pressure (systolic +10.2 ± 6.3 vs. +3.6 ± 9.8 mmHg; diastolic +9.6 ± 11.1 vs. +0.2 ± 2.1 mmHg;p = 0.02 for each); however, at steady-state the peak/trough differences in pressure between the methods were similar. Thirdly, compared under rest conditions, to random zero sphygmomanometer (RZO), the Finapres systolic pressure was higher (6.8 ± 3.5 mmHg) and diastolic pressure lower (–6.0 ± 1.9 mmHg). During upright bicycle exercise, the difference between the Finapres and RZO in systolic blood pressure increased at each level of exercise (+14.3 ± 4.2, +17.9 ± 4.0 and +22.2 ± 4.1 mmHg respectively at each exercise stage:p < 0.01). For RZO, diastolic blood pressure fell as exercise workload increased whereas Finapres diastolic blood pressure increased on exercise (3.1 ± 2.6, 7.0 ± 2.1 and 8.1 ± 2.0 mmHg respectively:p < 0.01). Thus there were systematic differences between the values recorded by the Finapres and proximal blood pressure methods and limited agreement in the rest to exercise increments related to light exercise. Calibration of the Finapres values in terms of the other methods is limited by the variable relationship to these related changes in arterial distensibility.     

EEG findings in hypomelanosis of Ito.

The EEG findings in 15 children with Hypomelanosis of Ito have been reviewed and related to the clinical and CT scan data. Although no consistent electroclinical associations were found in the group as a whole, there was some association between the presence of abnormal rhythmic EEG activity and the radiological appearances of neuronal migration defects. In addition, the possibility is raised that there may be a distinctive sub-group of children with Ito's syndrome who present with an early onset of intractable seizures and who have a neuronal migration defect.     

A new fluorescent mitochondrial antibody: Disease association

The case notes of 34 patients whose sera contained an antibody giving an unusual immunofluorescent staining pattern were reviewed. This antibody designated M2(1) gave a slightly different pattern of staining on composite sections of rat liver, kidney and stomach from the primary biliary cirrhosis associated M2 antimitochondrial antibody. Anaemia was present in 10 patients, endocrine disease in 7 patients and autoimmune liver disease in 6 patients. We did not find the presence of M2(l) antibody to be of specific diagnostic significance. Although the M2(l) antibody is rare, caution is required in order to avoid confusion between this antibody and the M2 antimitochondrial antibody of primary biliary cirrhosis.