Preventive effect of estrogen on postmenopausal bone loss.

Follow-up studies of bone mineral content in the radius were done in 82 postmenopausal women 4 to 10 years after the first examination. These patients were subdivided into four groups depending on the type of menopause (artificial or natural) and estrogen administration (treated or untreated). Bone mineral mass and combined cortical thickness decreased significantly in both groups of untreated women. Both mineral loss per year for the untreated women was -9.1 mg/sq cm for castrates and -6.9 mg/sq cm for those with a natural menopause. In neither group was the rate of loss correlated with age. The change in bone mineral mass per year in the estrogen-treated subjects (mean +3.25 mg/sq cm) differed significantly from that of untreated subjects (mean -7.99 mg/sq cm). The findings suggest that postmenopausal osteoporosis could be prevented by estrogen treatment.

Improved vertebral fracture threshold in postmenopausal osteoporosis by radiogrametric measurements: its usefulness in selection for preventive therapy.

Measurements of the combined cortical thickness at the midshafts of the second metacarpal and the proximal radius, as well as their sums, were made from fine-grained radiographs in 107 normal premenopausal and 227 postmenopausal women and in 57 women with at least two spontaneous vertebral compressions. The -2 SD level of the premenopausal women was found to be an excellent vertebral fracture threshold for the radius measuring site and for the sums of metacarpal and radial measurements. Only 2 of 57 (4%) and 3 of 57 (5%), respectively, of values in the vertebral compression group fell at or above this level. At -3 SD a "secondary fracture threshold" was found for the sums in that only 7 of 57 (12%) of values in women with vertebral compressions were above this limit, but -3 SD was less satisfactory for the radius. We conclude that this method discriminates as well between nonfracture and fracture cases as other radiologic methods for measurement of bone mass or density. Because it is less costly it seems better suited for mass screening in selecting postmenopausal women for preventive therapy than the less widely available high-technology methods.

Advantages of peripheral radiogrametry over dual-photon absorptiometry of the spine in the assessment of prevalence of osteoporotic vertebral fractures in women.

Since osteoporosis develops in most postmenopausal women and is probably the most important single factor in the pathogenesis of osteoporotic fractures of the spine, hip, and wrist (and at other sites), methods suitable for mass screening should be developed. In this study of 97 women aged 24-79, measurements of the lumbar spine mineral content by dual-photon absorptiometry (DPA) were compared with the summed combined cortical thickness measurements from radiographs of the radius and metacarpal II (MR). There was good correlation between the two methods (r = 0.90). The correlation of age with MR was higher than with DPA. The correlation of years postmenopause was significant with MR but not with DPA. Taking the -2 SD level of the premenopausal means to be previously established vertebral fracture thresholds, 24% of the DPA measurements, but no MR measurements in patients with vertebral compressions, were above the fracture threshold. Since MR measurement requires taking only two small plain radiographs using ordinary x-ray equipment, it is concluded that this less expensive method is better suited to screening for osteoporotic vertebral fracture risk in postmenopausal women than DPA.

Longitudinal microradioscopic comparisons on endosteal and juxtaendosteal bone loss in premenopausal and postmenopausal women, and in those with end-stage renal disease.

Endosteal bone resorption is the principal mechanism of bone loss in involutional osteoporosis and in renal osteodystrophy. In the cortical bone it is often accompanied by juxtaendostal bone resorption. Using fine-detail radiographs and x6 magnified viewing, longitudinal radiographic observations and measurements were made on these two forms of bone resorption in the metacarpals II, III, and IV in three groups of women: (1) premenopausal, (2) postmenopausal, and (3) patients with end-stage renal disease. Bone loss was found to be negligible in the premenopausal women, but in postmenopausal and renal patients both endosteal and juxtaendosteal bone resorption were frequently demonstrable. It is suggested that when a base-line fine-detail hand radiograph is obtained at the time of the menopause, follow-up radiographs may permit detection of relatively early endosteal and juxtaendosteal bone loss by comparing the respective areas in metacarpals with those of the original radiograph. Since the methodology does not require expensive equipment, has a low intraobserver error and is simple to perform, it may deserve to be further evaluated in studies aimed at developing a simple and inexpensive approach as a screening method for early detection of postmenopausal osteoporosis.

Comparisons between X-ray photodensitometric and gamma-ray absorptiometric findings of bone mineral measurements, and the evidence of their convertibility.

Fifty-two bone mineral measurements were made in chronic renal failure patients using two different radiologic techniques concurrently: gamma-ray absorptiometry; and x-ray photodensitometry. Although the sites of measurements of the cortical bone mineral mass in radius were different (distal vs. proximal) and different parameters were determined (in units of gm/cm vs. gm/cm2), a moderately good correlation was found between measurements by the two techniques (r = 0.61, p less than 0.001). Using external bone width, it was possible to calculate from photodensitometric measurements the bone mass per unit length (gm/cm). This conversion improved the correlation with absorptiometry values considerably (r = 0.78, p less than 0.001). A similar correlation was found between the trabecular bone mass in the distal radius, measured by absorptiometry, and the cortical bone mass in the proximal radius, determined by photodensitometry (r = 0.79, p less than 0.001), the correlation between the cortical and trabecular bone masses by absorptiometry being only slightly higher (r = 0.84, p less than 0.001). The residual variations not explained by the correlations between the absorptiometric and photodensitometric techniques may be largely due to the real differences of bone mineral masses at the two measuring sites and by the inherent methodological errors.

Partial body calcium measurements on patients with renal failure.

The bone calcium status of 39 patients with chronic renal failure on hemodialysis has been measured by in vivo neutron activation analysis (IVNAA) and reported in terms of a calcium bone index (CaBl) which relates the calcium in a patient to that in a normal person of the same height. In 20 of the 39 cases sequential measurements were made over periods of up to 40 mo. The results are compared with data obtained by radiology and by histological examination of bone biopsies. CaBl values varied from below normal to, in one case, above the range of normal. Many of the higher values were associated with demonstrable osteosclerosis. As found in previous work here with IVNAA, significantly low values of CaBl were associated with vertebral deformities; however, some patients with deformity had normal CaBl values, indicating that these had both local mineral loss (resulting in fracture) and osteosclerosis. Taken all together, the data suggest that more than half the patients have osteosclerosis. Sequential data showed no uniform response to treatment.

Long-term continuous ambulatory peritoneal dialysis in diabetics.

Of 147 diabetic patients with end-stage renal disease who were treated in our CAPD program between 1978 and 1991, 6 men and 1 woman (5 had type II and 2 type I diabetes) with a mean age of 54 (range 21-70) years have been on CAPD for more than five years (mean: 76 mos, range: 65-109 mos) and on peritoneal dialysis (IPD+CAPD) for an average of 85 (range: 67-118) mos. They had a variety of comorbid conditions at the start of CAPD: Retinopathy (5/7), blindness (3/7), hypertension (5/7), peripheral neuropathy (7/7), peripheral vascular disease (3/7), congestive heart failure (3/7), myocardial infarction (1/7), ischemic heart disease (2/7). Two were smokers and five over the age of 65. Peritonitis rate was 1 episode/11.4 pt mos, exit-site infection 1/76.4 pt mos and average hospitalization rate 32.8 days/patient/year. Hypertension was well-controlled with discontinuation of all medications; after initiation of CAPD two of them remained without medications throughout the study but in the rest, medications had to be restarted. As assessed by HbA1c, blood glucose control improved with IP administration of insulin. Residual renal function progressively decreased. None of them developed severe hyperparathyroidism. Peripheral neuropathy remained stable in four and deteriorated in two. Total protein, albumin, cholesterol and triglycerides decreased during the last two years indicating a degree of malnutrition. Our experience with these seven patients suggests that diabetic patients, even the aged and those with many comorbid conditions and complications, can survive for long periods on CAPD.

Quantitative radionuclide scanning in metabolic bone disease.

A simple method of quantifying skeletal uptake of 99Tcm-methylene diphosphonate, using a rectilinear scanner and a simultaneously image standard, is described. The pattern of quantified uptake in ten regions of the skeleton, the sacro-iliac joints and kidneys in 57 controls and 54 patients with various metabolic bone disease is presented. This method distinguishes patients with primary hyperparathyroidism and osteomalacia from controls with a sensitivity adequate for clinical purposes. In primary hyperparathyroidism the increased skull uptake of tracer correlated well with levels of serum alkaline phosphatase, plasma parathyroid hormone, urinary hydroxyproline excretion and the degree of intracortical resorption in the metacarpal bones. The skull uptake in oestoporosis was normal or moderately elevated and correlated well with bone mass density measurements of the radius. Patients with osteomalacia also showed the greatest increase in tracer uptake in the skull. Patients with thyrotoxicosis differed from most other patients by showing moderately increased uptake in shafts of long bones. We propose our method of quantitative bone uptake as a useful noninvasive test to detect metabolic bone disease and to monitor responses to therapy of bone disease.

Visceral calcification and the CaXP product.

The authors studied the presence of visceral calcification as evidenced by the visceral uptake of bone-seeking radionuclides during the course of a bone scan among 22 patients with terminal renal failure maintained on dialysis, nine patients with hypercalcemia secondary to malignancy, and nine patients with primary hyperparathyroidism. Uptake by the lungs or stomach was observed in 11 renal failure patients (50%) and in four of those with malignancy and hypercalcemia (44%). None of the patients with primary hyperparathyroidism had evidence of visceral calcification. The serum CaXP product was significantly higher among those with visceral calcification than those without. The results of this study indicate that a CaXP product of 60 represents the saturation product of calcium phosphate in serum above which spontaneous precipitation of this salt may occur in such viscera as stomach and lungs.

Oxalate bone disease--an emerging form of renal osteodystrophy.

Rosette-like arrays of highly birefringent calcium oxalate crystals are commonly seen in the marrow space of bone biopsy specimens taken from patients with primary hyperoxaluria, particularly if complicated by renal failure. Similar deposits have been described in chronic hemodialysis patients with secondary forms of oxalosis. Large multinucleated histiocytes may be seen surrounding these crystal deposits. Many of these cells are histologically indistinguishable from osteoclasts. We present a patient in whom this histiocytic reaction appeared to be of sufficient magnitude to stimulate bone resorption and to cause severe osteodystrophy. This observation, and those of other investigators reviewed in the discussion, suggest that oxalate deposition within bone may contribute to the pathogenesis of uremic osteodystrophy in chronic renal failure patients with primary or secondary types of oxalosis.

Radiologic study of endosteal, intracortical, and periosteal surfaces of hand bones in metabolic bone diseases.

In metabolic bone diseases, subtle abnormalities occur on the three surfaces of bone, the recognition of which is important for diagnosis, as well as in follow-up studies, to recognize progression or regression. These resorptive and formative changes are best studied in fine-detail hand radiographs under 6 to 8 times magnification by a relatively simple radiologic method (microradioscopy). The periosteal resorption of hyperparathyroidism is thus recognized earlier than by regular radiography, and intracortical resorption, not detectable by the naked eye, can be visualized. The latter is also seen frequently in nutritional osteomalcia, renal osteodystrophy, and thyrotoxicosis, and sometimes in acromegaly. Endosteal resorption in developing involutional osteoporosis can also be recognized more efficiently by microradioscopy than by ordinary radiographs without magnification. Fine-detail hand radiographs may thus be used as an inexpensive preliminary measurement for diagnosis of osteoporosis.