The effect of low-dose cyclical etidronate and calcium on bone mass in early postmenopausal women.

This 2-year study was carried out in 36 healthy women of mean age 53.9 +/- 3.8 (SD) years and 3.4 +/- 2.3 years postmenopausal. Bone mineral density (BMD) in the spine, measured by single-energy quantitative computed tomographic scanning, gave a mean initial value of 110 +/- 26 mg/ml. The women were divided randomly into group 1 (n = 11), calcium 600 mg/day; group 2 (n = 15), calcium plus etidronate sodium 400 mg/day for 14 days every 3 months; and group 3 (n = 10), calcium plus etidronate plus phosphate, the 14-day etidronate course being preceded by phosphate 1 g twice daily for 3 days. During the first year of the study BMD decreased by 6.0 +/- 5.8% (p < 0.005) in group 1 subjects and increased by 4.5 +/- 7.8% (p < 0.005) in the combined etidronate-treated groups (difference between control and treated p < 0.001). Inclusion of phosphate in the regimen did not affect the response to etidronate. In the second year there was no significant mean change in BMD in any of the three groups. However, whilst there was little change in BMD values for most of the group 1 subjects, there was considerable variation in individual response within the etidronate-treated groups, with some subjects gaining and some losing bone. The change in BMD during the second year in the subjects as a whole was highly correlated with the change in plasma calcium after 3 months of treatment (r = 0.60, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Measurement of osteoclasts and bone resorption by automated image analysis.

An automated image analysis method is described for measurement of osteoclasts and resorbing surface in calcified bone. Osteoclasts, osteoid, and mineralized bone were measured in a single section, reacted for acid phosphatase activity, and then stained with orange G and light green stain. Three images were acquired of each field with a monochromatic camera at illuminating wavelengths of 635, 540, and 480 nm (selected using a stage monochromator). These wavelengths were chosen according to the absorption spectra of the different image components to maximize absorption differences between osteoclasts (red), mineralized bone (blue/green), and osteoid (orange). These components were then discriminated according to operator-defined ranges of color density (mineralized bone) or color fraction (osteoid and osteoclasts). A gray level coded segmented image was produced, from which was determined the area, perimeter, and number of each component and the length of contact zones with the marrow and between these components. The method was evaluated by twice measuring 10 bone sections from patients with end-stage liver failure awaiting liver transplantation. The method was quite reproducible, with coefficients of variation varying between 4% for bone volume (% tissue volume) and 22% for osteoid surface (% bone surface). The sections were also measured using a previously established semiautomated method. Coefficients of variation between methods were higher varying between 4% for bone volume (% tissue volume) and 56% for osteoid volume (% bone volume). The automated method gave a substantial time saving compared to the semiautomated method. An interactive technique was used in adjacent sections to evaluate tetracycline labeling and osteoblast surfaces.

Osteocyte death and hip fracture.

The viability of osteocytes can be demonstrated in sawn decalcified sections of bone by their lactate dehydrogenase activity. In the cancellous bone of the femoral head, the proportion of lacunae containing viable osteocytes decreased from 88 +/- 7% (mean +/- SD) at 10-29 years to 58 +/- 12% (P < 0.001) by 70-89 years. Viability in the second lumbar vertebra was 88 +/- 3% in subjects aged 25-90 years and did not decrease with age. Mean osteocyte viability in the femoral head of 21 hip fracture patients aged 72-94 years was 58 +/- 21%, similar to controls of a similar age, though there was greater variation and, in five patients, osteocyte viability was less than 25%. In hip fracture patients, microfracture callus incidence correlated positively with osteocyte viability, with little or no fracture callus observed if the bone viability was low. Ultimate compressive strength did not correlate with osteocyte viability. In the femoral head there is gradual, age-related reduction in osteocyte viability that can be more pronounced in hip fracture. Osteocyte death may affect bone quality by impairing repair of fatigue damage.

Bone death in transient regional osteoporosis.

A 48-year-old man developed transient regional osteoporosis, with hip and later knee pain. He responded well to lumbar sympathectomy. The femur and tibia adjacent to the painful knee were osteoporotic, while the medial femoral condyle showed increased uptake in a bone scan. In the femoral condyle, bone histology showed areas of dead bone undergoing osteoclastic resorption, and increased bone formation. The tibial bone was histologically normal. The partial bone death in the distal femur suggests that the disorder may be related to both avascular necrosis of bone and reflex sympathetic dystrophy.

Treatment of Paget's disease of bone with a combination of intranasal salmon calcitonin and oral calcium and thiazide.

The purpose of this study was to establish the smallest dose of nasally administered salmon calcitonin (SCT) which, if given in conjunction with a previously published calcium/thiazide treatment, would be as effective as parenteral SCT in the treatment of Paget's disease of bone. Forty patients suffering from symptomatic Paget's disease were treated with 0.5 g calcium three times daily, 10 mg/day clopamide, and 400 IU nasally administered salmon calcitonin given once or twice weekly. This regimen was given for 5 months, after which all treatment was ceased for 4 months. Parenteral SCT (100 IU) was then given three times weekly for 5 months to 25 of the patients. With the oral/nasal treatment, the plasma alkaline phosphatase level (AP) decreased by 30 +/- 15 (SD)% when the SCT was given once weekly and by 39 +/- 11% (P less than 0.05) when the SCT was given twice weekly. There were similar decreases in the fasting urinary hydroxyproline:creatinine ratios. The parenteral SCT reduced the AP by 33 +/- 23%. Though reduction in bone pain was similar with both treatments, most patients preferred the oral/nasal treatment. It is concluded that the oral/nasal treatment, when the SCT is given twice weekly, has similar efficacy to parenteral SCT, and is a well tolerated, effective initial treatment for Paget's disease of bone.