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A rational approach to the diagnosis of osteoporosis by the primary care physician is outline, with emphasis on the patient who presents with chronic back pain and a vertebral compression fracture. The basic information includes data from the patient's history and physical examination, laboratory, x-ray and bone biopsy studies, and determination of bone mineral content (BMC) by photon absorptiometry. Characteristic radiologic features associated with bone loss, BMC changes, and bone biopsy findings are illustrated. This diagnostic approach, summarized in a flow diagram, poses a series of questions; the answer to each question leads either ot a diagnostic conclusion or to further questions which must be answered. This permits decision as to whether a compression fracture is due to trauma, local osteoporosis, osteomalacia, secondary osteoporosis or primary osteoporosis. In te study population (150 subjects), 80 percent of patients presenting with vertebral compression fractures had primary osteoporosis.

Absorptiometric measurements from multiple sites in 212 consecutive patients were examined to determine the interrelationships among bone mineral content values obtained from the lumbar spine, hip, and forearm. Dual photon absorptiometry was used to examine the spine, femoral neck, Ward's triangle, and greater trochanter while the radius and ulna were studied with single photon absorptiometry. All studies were performed on the same day. Concurrent measurements were available for the spine and hip in 197 patients, for the spine and forearm in 151 patients, and at all three sites for 146 patients. Variable degrees of correlation were found among the mineral content values from the six sites, with r values ranging from 0.40 to 0.93. The femoral neck and Ward's triangle showed the highest degree of correlation (r = 0.93); the ulna and lumbar spine demonstrated the poorest correlation (r = 0.40). Relationships between distant anatomic sites exhibited a large amount of variability (large standard error of the estimate) even when highly correlated. Useful predictions of bone mineral content could be obtained only for sites in close proximity. These results suggest that bone mineral content determinations in the upper extremities by single photon absorptiometry may not be useful for predicting mineralization in clinically more significant areas such as the lumbar spine and hip.

The traveling wave characteristics for a single compressive pulse were studied in fresh and embalmed human long bones. The stress wave was generated by the longitudinal impact of a steel ball on one end of a bone and was monitored by bonded strain gages. The dynamic properties, namely velocity, attenuation coefficient and dispersion were correlated with the mineral density, porosity, and cross-sectional area of the specimens. Statistically significant relationships were found between several of these parameters. These stress wave propagation characteristics are important for our understanding of the dynamic loading of bone and they may also provide a basis for the development of noninvasive techniques for studies of diseased or fractured bone.

Vitamin D deficiency is common in pregnant Asian women. The effect of maternal vitamin D deficiency on fetal skeletal mineralisation was assessed by measuring the bone mineral content of babies born to 45 Asian women, 19 Asian women who had received 1000 units of vitamin D during the last trimester, and 12 white women. The mean cord blood concentrations of 25-hydroxy vitamin D in the three groups were 5.9 +/- SE 0.9 nmol/l (2.4 +/- SE 0.4 ng/ml), 15.2 +/- 3.2 nmol/l (6.1 +/- 1.3 ng/ml), and 33.4 +/- 3.6 nmol/l (13.4 ng/ml), respectively. Despite this wide variation in values there was no significant difference in the bone mineral content (as assessed by photon absorptiometry) of the forearms of babies born to these women. This suggests that mineralization of the fetal skeleton is not impaired in maternal vitamin D deficiency. Craniotabes (skull softening) was present in seven of the 64 Asian babies. The bone mineral content in these babies was not significantly different from that of babies without this sign, and craniotabes should not therefore be taken as an indication of a generalized impairment in skeletal mineralization.

Results from a cross-sectional study showed the concentration of lead in the blood of male workers, aged 20-55 years, occupationally exposed to lead in a steel factory, to be negatively correlated with the daily nutritional content of dietary fiber, iron and vitamin B1 (thiamine) intake. Furthermore, in experiments with rats injected subcutaneously with lead acetate, lead levels in blood and femur of animals on a vitamin-rich laboratory chow were lower than those fed a general laboratory chow. Moreover, in the group fed the vitamin-rich chow, lead excretion in feces increased, while excretion in urine did not. These results suggest that lead excretion from the body may be increased by a high intake of nutrients such as thiamine, iron and fiber, that lead excretion in feces via bile may be enhanced by a large intake of vitamins such as thiamine and that accordingly the lead concentration in the blood of the workers is reduced.

Dual-photon absorptiometry using 153Gd (44 and 100 keV) was used to measure the bone mineral content (BMC) of the trunk and of the total body (TBBM) in 7 volunteers with no overt bone disease. These values were compared to those obtained with partial-body neutron activation of calcium (trunk Ca). The trunk Ca seemed to represent best a 60 x 30 cm area; the correlation coefficient with the corresponding BMC in that area was 0.97 (SEE congruent to 7%). Trunk Ca was also highly correlated with TBBM (r = 0.96; SEE = 8%) and with radius BMC (r = 0.92; SEE = 11%), but the correlations with the BMC of smaller subareas of the trunk were lower (r congruent to 0.9; SEE approximately 12%). The BMC of the lumbar spine was only moderately correlated with trunk Ca, radius BMC and TBBM (r approximately 0.82; SEE approximately 18%), and only slightly more associated with trunk BMC (r approximately 0.88; SEE approximately 14%). The BMC of the combined lumbar-thoracic spine showed higher correlations with trunk Ca, radius BMC and TBBM (r approximately 0.87; SEE approximately 13%), and trunk BMC (r = 0.93; SEE approximately 10%). An accurate and sensitive measure of spinal status requires a direct measurement of that area.

Beagle dogs 3-7 years old were ovariectomized (n = 9) or sham operated (n = 6) and followed for 48 weeks with measurements of body weight, tibial shaft bone mineral content (BMC), and serum biochemistry. Following killing, measurements were made of bone strength and histomorphometry. Ovariectomy (OX) significantly reduced serum estrone and estradiol concentrations and their variability from month to month. There was a transient decrease in cortical BMC of the OX dogs during the first 12 postoperative weeks but no difference between the groups after 48 weeks. Serum osteocalcin was elevated, but there was little effect on serum alkaline phosphatase, Ca, P, or calcitonin. OX increased the number of tetracycline-labeled osteons in cortical bone but reduced the percent trabecular surface labeled with tetracycline. OX produced no significant changes in the composition of the bones or loss of cortical area, but a statistically significant 15% trabecular bone loss occurred in the spine. However, bone strength had not been significantly affected at the time of sacrifice.

This study investigated the effect of metastatic prostatic carcinoma on bone density. Thirty patients underwent a lumbar spine scan with a dual photon absorptiometer. Of these patients, 9 had proven skeletal metastatic deposits in the area being investigated. Comparison of results with a non-matched control population with proven benign prostatic histology showed a significantly elevated linear bone mineral content (BMC) in the disease group. Patients scanned after a 3- or 6-month period of hormonal therapy demonstrated a rise in BMC values, although the trend was not statistically significant. Indices of calcium metabolism have also been investigated.

1. Oral administration of EAA and calories was demonstrated to improve nutritional status of chronic stable hemodialysis patients. 2. This improvement was manifested by an increase of hematocrit, total protein, serum albumin, transferrin, and TLC in those patients with low values, as well as an increase in cortical and trabecular bone thickness. 3. Improvement occurred in patients receiving a diet with one gm protein/kg/day. 4. Administration of calories without EAA did not show any beneficial effect.

Patients put at bedrest for medical reasons lose 1-2% of spinal bone mineral per week. Losses of this magnitude during even short-term space flights of a few months would pose a serious limitation and require countermeasures. The spinal bone mineral (L2-L4) was determined in 6 healthy males (precision = 2%) before and after 5 weeks of complete bed rest. Only one individual had a significant loss (3%) and the -0.9% mean change for the 6, was not significant (P = 0.06). The average negative calcium balance during the 5 weeks was 4 g or 0.36% of total body calcium, similar to that reported in other bed-rest studies. Spinal bone loss, however, in healthy bed-rested males is significantly less than reported for bed-rested patients, suggesting that a large loss of spinal bone mineral does not occur during space flight missions lasting 5 weeks or less.

Images of the distribution of a given nuclide in a section of biological tissue can be obtained at the microscopic level by "secondary-ion mass analysis." In this method, the images are formed by an ion-emission microscope wherein the specimen's atoms are progressively sputtered from the surface and the ions are selectively visualized by mass spectrometry according to their mass-to-charge ratios. Such images are obtained at the cost of the destruction of the specimen, which is progressively eroded at the rate of 1-10 atomic layers per second. The spatial resolution is better than 1 micrometer for an imaged area 250 micrometer in diameter and a section thickness of 1-2000 nm; thus, the analytical images are element distributions representative of 3-6000 atomic layers. Distributional images can be obtained for many nuclides, whether stable or radioactive, natural or artificially administered.

Collagen in the muscles of fish constitutes the main component of the connective tissue membranes joining individual myotomes and is responsible for the integrity of the fillets. The content of collagen in fish muscles is from about 0.2 to 1.4% and in squid mantel about 2.6%. Fish and invertebrata collagens contain slightly more essential amino acids than intramuscular bovine connective tissue collagen. The invertebrata collagens are exceptionally rich in sugars linked mainly O-glycosidically to hydroxylysine residues. During maturation of fish the proportion of collagen to total protein in the muscles increases while the extent of crosslinking does not change significantly. The thermal properties of fish collagens depend significantly on the content of hydroxyproline and proline residues which in turn is correlated to the temperature of the habitat. Generally the shrinkage temperature of fish skin collagens is about 20 degrees C lower than that of mammalian hide collagens. In several species of fish the weakening of the connective tissues post mortem may lead to serious quality deterioration that manifests itself by disintegration of the fillets, especially under the strain of rough handling and of rigor mortis at ambient temperature. Thermal changes in collagen are the necessary result of the cooking of fish, squid, and minced fish products and contribute to the desirable texture of the meat. However, they may lead to serious losses during hot smoking due to a reduction in the breaking strength of the tissues when heating is conducted at high relative humidity. Because of the high viscosity of gelatinized collagen, it is not possible to concentrate the fish stickwaters, a proteinaceous byproduct of the fish meal industry, to more than 50% dry matter. Better knowledge of the contents and properties of fish collagens could be helpful in rationalizing many aspects of fish processing.

Histochemical studies and electron probe x-ray microanalysis for aluminium have been performed on 16 samples of undecalcified bone from cases of renal osteodystrophy associated with a syndrome suggestive of dialysis encephalopathy (five cases), age and sex matched controls for these and a group of patients with chronic renal failure (six cases) who have never been on haemodialysis. Aluminium was detected only in the patients with a dialysis encephalopathy-like syndrome. This group had significant histological bone disease the features of which were broadly consistent with the so-called atypical renal osteomalacia which is thought to be due to a metal toxin. Aluminium was demonstrated at the interface between osteoid and mineralised tissue--that is, at the site of the calcification front, where it could interfere with the mineralisation process. In the group of patients who had never been subjected to haemodialysis there was also significant histological bone disease but no evidence of aluminium accumulation. In this group the bone disease was of a more typical pattern of osteomalacic changes coupled with those of hyperparathyroidism.

It has recently been demonstrated that calcium ionophore A23187 mimics certain of the effects of parathyroid hormone (PTH) on bone in vitro, including stimulation of 45Ca release and cAMP formation. To further examine the relative effects of these two agents on bone cell metabolism, we compared the effects of synthetic PTH 1-34 (50 ng/ml) and calcium ionophore A23187 (0.5 micrograms/ml) on 45Ca release, DNA concentration, and nucleic acid synthesis in fetal rat forelimb rudiments cultured for periods up to 120 h. Both agents stimulated 45Ca release; however, the effects of PTH were apparent after a shorter period of exposure. Bone DNA concentration (expressed as microgram DNA/mg bone) was not affected by PTH but was significantly increased relative to control values by exposure to A23187 for 8-120 h of incubation. PTH increased the incorporation of 3H-thymidine into DNA at 30 and 48 h, and increased the incorporation of 14C-uridine into RNA at 48 h, time points which corresponded to a period of accelerated PTH stimulation of 45Ca release. In contrast, 3H-thymidine and 14C-uridine incorporation were both uniformly suppressed by A23187 at all time points examined. Thus the increased DNA concentration observed in A23187-treated rudiments appeared to be the result of a decreased rate of bone maturation and mineralization. The markedly different patterns of nucleic acid synthesis in response to PTH and A23187 suggest that these agents differ significantly in their mechanisms of action on bone cell metabolism.

Neutron activation analysis was employed to determine total body calcium in C3H/St (Ha) female mice. Ninty-nine percent of total body calcium is in bone and loss of calcium was used as an index of osteoporosis. Heparin (500 U/kg B.I.D.) treatment for three months resulted in significant osteoporosis. Both human and salmon calcitonin (4 MRC U/Kg B.I.D.) prevented heparin induced osteoporosis. The results suggest that calcitonin may prevent pathological fractures in patients on anticoagulants and other osteoporosis inducing regimens.

A number of different techniques are available to study bone mineral. Those based on radiographs are helpful as an initial approach to the symptomatic patient with advanced disease, but they do not have the sensitivity to detect early bone loss, to assist in the estimation of fracture risk, or to monitor effects of treatment in controlled drug studies. A radiograph of the spine and hip, however, should be the first step before other tests are ordered. Photon absorptiometry methods or CT-based tests are currently most attractive as second-line approaches. Of these, photon absorptiometry is more widely tested clinically and allows studies of predominantly cortical or trabecular bone sites and total skeletal calcium. Although all of this cannot be done reliably with one instrument under routine laboratory conditions at present, it may well become possible in the near future. Of the CT-based procedures, the forearm scanner is very attractive because of its high precision and accuracy and the fact that it allows measurement of trabecular bone only. The technique is restricted to the forearm and may not be versatile enough for modern clinical requirements. A similar comment may be applicable to neutron-activation techniques of the hand, forearm, or spine. Low-level counting and the handling of neutron sources are not widely known techniques in many laboratories, and this will restrict their use in clinical practice. At this time there is no optimal technique available for mass screening for early osteoporosis. Dual-photon absorptiometry of the spine has been in use in our institution as the method of choice in selected patients for early detection of osteoporosis. However, for screening purposes the radius is still a very attractive bone to measure. At the currently used measuring sites, however, it does not have the sensitivity required to indicate spinal bone loss. Perhaps measurements closer to the distal end, where the trabecular-to-cortical bone ratios approach that in the spine, could be more sensitive. The difficulty of relocating the arm for photon absorptiometry can perhaps be solved for photon absorptiometry, or may be resolved by CT of the forearm. Correlation of the extreme distal radius with the spine is necessary to answer this question.

Double photon absorptiometry comparison was done of lumbar bone mineral content (BMC) values in 40 women with well-compensated non-insulin-dependent diabetes mellitus (type II) and on dietary and/or oral hypoglycemic treatment, and 35 age-matched non-diabetic women, to determine the presence and degree of osteoporosis in this type of diabetes by means of a highly precise and sensitive method. No difference between the two groups was noted as regards blood calcium, phosphorus, PTH and thyrocalcitonin, and urinary calcium and phosphorus. BMC, on the other hand, was significantly lower in the diabetics, both in L2,L3,L4 and in L4 alone. No significant difference could be discerned between patients on diet and those on drugs. It can thus be maintained that osteoporosis is a possible complication of type II diabetes and may appear even in the absence of its classical complications.

Mezlocillin and oxacillin have been used in combination for short-term antibiotic prophylaxis in orthopedic surgery. Antibiotic concentrations were measured in serum, wound secretions from subcutaneous tubings and bone. Half an hour after the i. v. application of 4 g mezlocillin + 2 g oxacillin, the concentrations in wound secretions were 20% of the serum levels. After four hours the levels of both antibiotics in wound secretions increased to 2.66 times the serum levels of mezlocillin, and 5.37 times those of oxacillin. After eight hours the concentrations in wound secretions dropped to about one half, but remained well within therapeutic levels. The parallel course of the concentrations of both antibiotics in wound secretions indicates that mezlocillin and oxacillin have very similar half-lives in wound secretions, although the serum half-lives (t 50% beta) of the two antibiotics are different. The concentrations obtained from cancellous bone were approximately. 10% of the serum levels one to two hours after the antibiotic infusion.

Energy dispersive X-ray microanalysis (EDX) (or electron microprobe analysis) of the relative intensity for calcium in different bone trabeculae from the tibia epiphysis, and in different parts of one and the same trabecula, was performed on 3 patients who had earlier had a fracture of the ipsilateral tibia-diaphysis. The variation in intensity was compared with the histochemical patterns obtained with both the Goldner and the von Kóssa staining techniques for detecting calcium in tissues. Previously reported calcium distribution features, found to be typical for posttraumatic osteopenia, such as striated mineralization patterns in individual trabeculae and large differences in mineralization level between different trabeculae, could be verified both by means of the two histochemical procedures and from the electron microprobe analysis. A pronounced difference was observed, however, between the two histochemical staining techniques as regards their sensitivity to detect calcium. The two methods have different turnover points, from negative to positive along a gradient change of calcium concentrations. To judge from the values obtained from the EDX measurements, the sensitivity of the Goldner technique should be more than ten times higher than that of von Kóssa. The EDX measurements gave more detailed information than either of the two histochemical techniques: great variations in the intensity of the calcium peak were found in trabeculae stained as unmineralized as well as mineralized.

Thirty-one patients scheduled for long-term (24 weeks) treatment with prednisone in comparatively high doses were randomly allocated to two further treatment groups. Group A received prednisone plus 'triple-treatment' (vitamin D2 45000 iu twice weekly, sodium fluoride 50 mg and calcium phosphate 4.5 g daily), group B received only prednisone. The study was undertaken in order to evaluate the effect of prednisone- and triple-treatment upon bone mineral content (BMC) and vitamin D metabolism. The groups were comparable with regard to age, sex and prednisone dose. BMC fell rapidly and similarly in both groups, demonstrating that the triple-treatment has no preventive effect on corticosteroid induced osteopenia. Serum concentrations of 25OHD2, 25OHD3 and 1,25(OH)2D were unchanged in group B (without triple-treatment), whereas in group A 25OHD2 increased enormously, 25OHD3 was suppressed possibly by substrate competition for hydroxylation in the liver and 1,25(OH)2D was halved. The suppression of 1,25(OH)2D may be an effect of raised 25OHD2 alone, or in combination with corticosteroid excess.

We have studied the effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on bone mass and bone mineral appositional rate in intact rats and rats with inflammation-mediated osteopenia (IMO), where osteoblast number and mineral appositional rate are decreased. 1,25(OH)2D3 prevents IMO-specific bone loss when given in a daily dose of 25 ng per rat, but does not when given in higher doses. The hormone was effective, when given over the complete duration of the experiment (21 days), but not when given over shorter time periods (7 and 14 days, respectively). 1,25(OH)2D3 prevents IMO-dependent reduction in mineral appositional rate and leads to an only moderate increase in intact rats. We conclude, that 1,25(OH)2D3 is more effective in stimulating mineral appositional rate in rats with IMO where mineral apposition is impaired.

Previous epidemiologic studies associated large differences of esophageal cancer risk with the nature of the staple diet. In this study, various cereals and dietary staples were fed to inbred BD IX rats for 7 months or longer. N-Nitrosomethylbenzylamine [(MBN) CAS:937-40-6] was given five times subcutaneously between the 45th and 58th day. The percentage of rats with tumors and the mean number of tumors per esophagus were similar when corn, wheat, commercial bird-resistant sorghum, bananas, and polished rice were fed but were strikingly lower when the basis of the diets was millet, red sorghum, brown rice, or potatoes. The number of esophageal tumors was significantly related to the dietary concentration of some minerals and vitamins. Supplementing marginally deficient corn or wheat diets with various combinations of nicotinic acid, riboflavin, zinc, magnesium, molybdenum, and selenium significantly reduced the numbers of esophageal tumors. When the feeding of protective cereals or nutrients was commenced only 150 days after MBN was given, a marked inhibitory effect on the progression of tumors was still observed.

The authors give an account of their experience with the assessment of group substances from skeletal remnants of historical persons and Egyptian mummies. They also draw attention to possible pitfalls of examinations and the interpretation of results.

Ca-acidic phospholipid-PO4 complexes promote in vitro hydroxyapatite nucleation and/or growth and are believed to have similar functions in vivo. The complexed acidic phospholipid content of human bones has been studied in femoral heads obtained at surgery from patients with osteonecrosis and osteoarthritis and compared with age-matched, disease-free control bones. The content of Ca-acidic phospholipid-PO4 complexes was elevated in bones that were judged on the basis of radiographic and histological data to be actively making new bone. These data suggest that the relative concentration of Ca-acidic phospholipid-PO4 in bone may be related to the rate at which bone is being made and mineralized.

1. During a 15-month period, 110 elderly patients admitted with fractured neck of femur were studied in comparison with 72 elderly control patients undergoing elective surgery admitted over the same period to the same orthopaedic wards. 2. A striking finding was the marked similarity of all variables measured in the fracture and control groups. The principal differences between the two populations were that the fracture patients had a lower mean forearm bone mineral content, and that their serum concentrations of albumin, globulin and phosphate were reduced. 3. Neither measurements of radioisotopic calcium absorption, nor those of the serum concentrations of calcium, 25-hydroxy-vitamin D3 nor alkaline phosphatase provided satisfactory discrimination between the groups. 4. Several indices were devised, based on linear combinations of the test results obtained, in an attempt to predict the liability to future fractures of patients being considered for prophylactic therapy with oestrogens or other drugs. However, further work is required to define an index of improved predictive power and to evaluate it prospectively.

Study Objective: To determine if a single bone mass measurement of the radius is predictive of future fractures at any site., Design: Observational study of a cohort of free-living subjects and a cohort of retirement-home residents with an average follow-up of 6.7 years and 5.5 years, respectively (range, 1 to 15 years for both cohorts)., Setting: General community and a retirement home., Subjects: Volunteer sample of white women (386 free-living and 135 living in a retirement home) who were free of disease and were not receiving medication known to affect bone metabolism. In terms of physical condition subjects ranged from the totally independent to the wheelchair-bound., Measurements and Main Results: A radial bone mass measurement was done at the initial visit. Subsequent non-spine fractures were reported by the subjects at follow-up visits, which were less than a year apart in most cases, and verified with medical records. Cox regression was used to model time to first fracture as a function of age and bone mass. These analyses showed that for every 0.1 g/cm decrement in bone mass, the relative risk of fracture was 2.2 (CI, 1.7 to 2.8) for the free-living and 1.5 (CI, 1.2 to 1.9) for the retirement-home residents. Baseline age did not predict the risk of fracture in either cohort, and controlling for baseline age did not reduce the relative-risk estimates of bone mass. Similar analyses also showed that bone mass was a statistically significant predictor for first hip fractures (n = 30) among the nursing-home residents (relative risk, 1.9; CI, 1.4 to 2.7) and first forearm fractures (n = 10) among the free living (relative risk, 3.6; CI, 1.9 to 6.8). For both cohorts, the 8-year probability of any nonspine fracture was about 80% for subjects with initial bone mass less than 0.6 g/cm and was less than 10% for subjects with initial bone mass greater than 0.8 g/cm. Similarly, those in the retirement home with bone mass below 0.6 g/cm had a 6-year probability of hip fracture of 43%, compared with a 17% risk for those with greater bone mass., Conclusion: A single bone mass measurement of the radius is predictive of future nonspine fractures at all sites, and at both the forearm and the hip. Baseline age was not a significant predictor of fracture within either cohort. Relative-risk estimates were not dissimilar across fracture sites.

We have previously reported an increase in forearm bone mineral content (BMC) during therapy for osteoporosis with the anabolic steroid, nandrolone decanoate. However, it has recently been claimed that part of this increase is spurious, due to a decrease in forearm fat during the treatment. We have therefore analyzed the data from a cross-over study of the effects of this agent on 70 osteoporotic women, using the fat correction procedure supplied by the manufacturer of the forearm densitometer. There was a significant rise (p less than 0.001) in the mean fat-corrected BMC (BMC[fc]) on nandrolone decanoate (50 mg intramuscularly every 2 or 3 weeks) and a non-significant fall in mean BMC[fc] off the drug. The mean time-weighted rate of change in the fat-corrected value was +29 +/- 5 mg/cm/year on nandrolone decanoate and -5 +/- 5 mg/cm/year off nandrolone decanoate (p less than 0.001). Nandrolone decanoate produces a significant gain in forearm mineral content even after allowing for changes in forearm fat content during therapy.

Bone mineral content (BMC) was measured annually over a three year period in 31 consecutive patients on maintenance hemodialysis (HD). No patient had received treatment with vitamin D derivatives, anticonvulsants or corticosteroids, nephrectomy or a renal transplant. Initial median BMC value in per cent of sex and age matched normal mean was significantly decreased to 91.0% (P less than 0.01), indicating bone mineral loss in chronic renal failure prior to HD. During HD a highly significant fall in mean BMC (in per cent of initial value) continued to 95.1%, 92,7% and 90.8% after 1, 2 and 3 years, respectively, with no influence of age, sex or initial BMC value. The interindividual variation in BMC changes, however, was considerable: the BMC loss over 3 years exceeded 10% in 13 (42%) patients ("rapid losers") while 12 (39%) patients had a BMC loss below 5%, or no loss at all. The "rapid loser" group had significantly higher serum levels of parathyroid hormone and alkaline phosphatases and, moreover, developed a lower serum phosphate and calciumXphosphorus product than the other group of patients ("slow losers"). The mean BMC loss over 3 years of HD was pronounced and significant (P less than 0.02) in patients with chronic pyelonephritis (9.8%) and polycystic kidney disease (14.2%), but much smaller, and not significant, in patients with chronic glomerulonephritis (4.8%). It is concluded that a selection of patients with a high degree of bone mineral loss during HD is not possible by means of sex, age, initial BMC, biochemical parameters, or diagnosis (2 patients with chronic glomerulonephritis appeared to be "rapid losers"). For that purpose a high-precision BMC method is mandatory.

Young male rats were exposed to repeated heliox dives and analyzed for skeletal alterations. Animals were exposed 1, 3, 5, or 7 times to either 1 ATA He-O2 for 12.5 h, or to 5 ATA He-O2 for 4 h and a 8.5 h decompression, or to 5 ATA He-O2 for 4 h and a 1.5 h decompression. In a separate study, 30 rats were exposed 6 times to 5 ATA He-O2 and explosively decompressed. Animals were sacrificed 20 d after the last dive. There were no significant changes in femur wet weight, density, ash weight, length, or mineral content. Plasma calcium, phosphorus, and alkaline phosphatase remained normal. Eighteen of 30 animals survived the six explosive decompressions; however, there were no significant changes in bone. These results indicate that the number and rate of decompressions used in this study have no lasting effect on bone growth and mineral composition in the rat.

1. Bovine articular cartilage slices were studied in long term culture by periodically pulse-labelling the cultures with radiolabelled precursors of glycosaminoglycans and isolating the glycosaminoglycans from cartilage. 2. Pretreatment of the cartilage slices with bacterial collagenase resulted in stimulation of the incorporation of radioactivity into the glycosaminoglycans. 3. The addition of a fraction from bovine bone, enriched in "matrigenin" activity, to cultures of cartilage pretreated with collagenase resulted in an additional increase in the stimulation of incorporation of radioactivity.

Twenty epileptic outpatients, aged 5-20 years and taking either phenobarbital or phenytoin for anticonvulsant therapy, were evaluated for femoral neck area bone mineral content and bone mineral density using dual photon absorptiometry. Duration of treatment averaged 51.4 months (range, 9-124 months). A group of 20 normal children who were matched for age, sex, and race served as controls. There were no statistically significant differences between the femoral neck area bone mineral densities of the epileptic patients as compared to the controls. There were also no correlations between duration of anticonvulsant therapy and bone mineral density, nor any differences in bone mineral density values when comparing epileptic patients taking phenobarbital with those patients taking phenytoin.

The concentrations of Fe, Zn, Mn, Cu, Pb, Cd, Co, Ni, Cr and Ag in 88 samples of various bones and five samples of trachea prepared from scaup ducks (Aythya marila L.) have been determined. With the exception of lead, no significant sex-related differences were observed for the concentration of metals. However, there were significant differences in the concentrations of most metals for different bones.

Pulse polarography has been applied to the determination of aluminium in bone. The sensitivity, selectivity and reproducibility of the method are described. The results of bone aluminium concentrations in controls and in haemodialysed patients treated with aluminium compounds are discussed. Pulse polarography permits very precise measurements of aluminium impregnating bone.

Bone mineral content (BMC) was measured by photon absorptiometry in fresh bone specimens: 35 iliac crest and 39 forearms were used. BMC was related to ash weight, fat-free weight and the amount of bone determined by quantitative histologic methods. Ninety-five per cent of the variation in bone mineral concentration (BMC') in the iliac crest could be explained by variation in ash weight, and 88% of the variation in BMC in the forearm could be explained by variation in the amount of bone determined histologically. The total cross-sectional bone area of radius and ulna could be calculated from the width of the structures measured on the photon absorption curves. Using this parameter and the relation between BMC and ash weight, the actual in-vivo bone mineral content in the forearm could be expressed in terms of ash-weight in grams per cm3 of total bone.

Metallic chambers were implanted into the proximal tibiae of rabbits to permit microscopic examination of living bone in situ. The bone repair process secondary to the injury produced during installation of the chamber, was visualized. Six to 8 weeks after implantation, osteoid and/or bone could be seen. The effects of various doses of disodium ethane-1-hydroxy-1, 1-diphosphonate (EHDP) on the repair and regeneration processes following chamber implantation were studied. Data from various techniques indicated that: (1) following low dose EHDP (0.25 mg/kg/day) chambers contained bone tissue morphologically and ultrastructurally indistinguishable from controls; and (2) with higher doses of EHDP (2.5 or 10 mg/kg/day) chamber contained spicules of normal osteoid, osteoblasts and osteocytes, but were devoid of osteoclasts. The effects of the various regimes of EHDP also were assessed on regenerated, trabecular bone contained within the tibia chambers three months after implantation of the chambers. Data from various methods of analysis supported the following conclusions: (1) the low dose of EHDP (0.25 mg/kg/day) had no toxic effects on the trabecular bone within the chambers but there appeared to be an increase in bone formation as compared to saline control; (2) higher doses of EHDP (2.5 or 10mg/kg/day) were not toxic to bone cells but thick osteoid seams formed on the trabecular bone within the chambers. No osteoclasts were found associated with the bone apparently due to the coverage of bone surfaces by osteoid seams; and (3) osteoid which accumulated after EHDP treatment of 2.5 mg/kg/day for 2 months remained uncalcified for as long as 2 months following withdrawal of EHDP administration. The results showed the value of tibial chamber for examining microscopically living bone in situ and demonstrated the inhibitory effect of EHDP on mineralization of newly formed osteoid and a lack of effect on bone cells.

In previous works we have studied the time of death of bone residuals through the following parameters: total lipids, triglicerides , cholesterol, free fatty acids, total proteins, zinc, iron, manganese, and phosphorus. These elements were quantified in groups of recent bones of 1 and 2 years and of 10, 15, 18, and 20 years postmortem. In this present work we are putting these results under statistical analysis consisting of a stepwise regression. This program selects and introduces in the regression the element that shows the highest correlation with the time of death. In successive steps the partial correlations between the date and the elements not already included in the regression are studied, while keeping the effects of the elements already included fixed. As a result we put forward three formulas in which the time of death appears linked with the parameters that define it best. In the first the time of death of the bones Y is estimated according to the protein X1 Y = 40.0014 - 7. 4275X1 In the second formula the time of death Y, is estimated according to proteins X1 and triglicerides X2. Y = 45.5970 - 10. 8096X1 + 0. 4104X2 And in the third formula the time of death Y is estimated according to proteins X1, triglicerides X2, and cholesterol X3. Y = 52.2032 - 7. 8213X1 + 0. 6355X2 - 3.4930 In the three formulas the coefficients of the correlation between the time of death and the variables are improved when the logarithms of the variables are taken, instead of the original measurements.