Healing of rachitic lesions in chicks by 24R,25-dihydroxycholecalciferol administered locally into bone.

In an attempt to further define the nature of the active metabolite in bone formation, a series of experiments were conducted whereby vitamin D metabolites were administered locally in vivo into the proximal epiphyseal growth plate of the tibiae of rachitic chicks. Local administration of 3 micrograms of 24,25(OH)2D3 in vivo to D-deficient chicks resulted in disappearance of the rachitic lesions in the same leg. Administration of 1 microgram 1,25(OH)2D3 in a similar manner failed to show any sign of healing. Injection of 5 micrograms 25(OH)D3 was followed by recovery from rickets in both the injected right leg and in the vehicle-injected left tibia, although the recovery was more pronounced in the injected leg. Lower doses of 0.3 or 1 microgram 24,25(OH)2D3 failed to reverse the rachitic lesions and induced only minimal recovery. These findings suggest that 24,25(OH)2D3 at the higher doses has a direct local effect on cartilage and bone, while 1,25(OH)2D3 has no such effect in chicks. 25(OH)D3 is probably absorbed from the epiphyses into the blood stream and converted into the active metabolites, which were indeed detected in the blood to exert its systemic effects.

Osteoporosis as the sole presentation of bone marrow mastocytosis.

Three (young) adults with severe generalized osteopenia and vertebral compression fractures were studied. Extensive clinical and laboratory investigations were not contributory. Undecalcified bone biopsies demonstrated multiple mast cell granulomas in the marrow in two patients and numerous mast cells diffusely distributed throughout the bone marrow in the third patient. Mast cells may serve as a pathogenic agent in osteoporosis. Therefore, we conclude that isolated skeletal mastocytosis without clinical evidence of mast cell mediator release should be sought in the evaluation of a patient with unexplained severe bone loss.

The metabolism of vitamin D3 during fracture healing in chicks.

The metabolism of vitamin D3 was studied in chicks after experimental fractures were performed on their tibiae. The chicks were fed for 3 weeks a vitamin D-deficient diet but were supplemented with radioactive labeled vitamin D3. The chicks were then divided into two groups. In the first group the right tibia was fractured, whereas the second group served as nonfractured control group. During the following days of fracture healing, the metabolites of [3H]vitamin D3 were measured in callus, epiphysis, diaphysis, plasma, duodenum, and kidney. Histological examination of calluses and bones, measurements of intestinal absorption of calcium, and renal production of dihydroxylated metabolites of vitamin D3 were performed as well. The levels of the dihydroxylated metabolites were increased in the calluses and the levels of [3H]24,25-dihydroxyvitamin D3 were found to coincide with the formation of cartilaginous tissue and with the renal production of this steroid. In the duodenum of the fractured chicks, the levels of [3H]1,25-dihydroxyvitamin D3 dropped significantly during the first week after fracture, coinciding with reduction in the intestinal absorption of calcium. In the plasma during those 3 weeks of healing process the levels of [3H]1,25-dihydroxyvitamin D3 were far below normal. These findings indicate that during the process of fracture repair, changes in the metabolism and expression of vitamin D are taking place in order to meet the new requirements of the body under stress condition of skeletal fracture.

Stress fracture of the tibia after arthrodesis of the ankle or the hindfoot.

We studied twelve patients who had a stress fracture of the tibia and one patient who had a stress fracture of the fibula after arthrodesis of the ankle or the foot. A second stress fracture subsequently developed in two patients. All but two patients were managed non-operatively, and the fractures healed uneventfully. One patient who was managed operatively had a below-the-knee amputation to treat a painful non-union of a tibial fracture, and the other had interlocking intramedullary nailing for a displaced fracture. All but one of the arthrodesis sites had fused before the stress fracture occurred. All of the stress fractures that occurred after arthrodesis of the ankle were in the middle and distal aspects or the distal aspect of the tibia, while those that occurred after triple arthrodesis were in the distal aspect of the fibula or the medial malleolus. Although six of the thirteen patients still had uncorrected alignment and deformity after the arthrodesis, optimum alignment after the arthrodesis did not preclude the occurrence of a stress fracture. We conclude that stress fracture must be considered in the differential diagnosis of pain months or even years after solid fusion at the site of an ankle or triple arthrodesis.

Successful high-dose calcium treatment of aluminum-induced metabolic bone disease in long-term home parenteral nutrition.

A patient who developed severe metabolic bone disease is presented. He had received long-term home parenteral nutrition (HPN) following extensive small bowel resection after mesenteric vein thrombosis. Bone disease caused by aluminum intoxication had components of osteomalacia and low-turnover osteoporosis. Aluminum was detected at the surface of mineralized bone and was elevated in the serum, resulting in a positive deferoxamine infusion test. One year of treatment with high doses of calcium (up to 24 mEq per day) significantly diminished the patient's bone pain, increased the serum levels of calcium, abolished aluminum deposits in the mineralized trabecula, improved bone formation, and increased trabecular bone volume as assessed by repeated histomorphometric analysis.

Levels of active metabolites of vitamin D3 in the callus of fracture repair in chicks.

The levels of the active metabolites of vitamin D were measured in the callus and in the epiphyseal growth plate of chicks given radioactive cholecalciferol during fracture healing. Those levels were correlated with the histological findings. Three groups of chicks were studied: a control group with no fracture, chicks with fractures fixed by Kirschner wire, and chicks with unfixed fractures. A significant increase in the levels of the active metabolites was found in the callus during the first few days after fracture. The levels of 25-hydroxycholecalciferol [25(OH)D3] and of 24,25-dihydroxycholecalciferol [24,25(OH)2D3] were higher when there was no fixation, while those of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] were higher after fixation. The concentrations of these metabolites in the proximal epiphysis of the tibia were similar to those found in the callus. Based on these findings it is suggested that the active metabolites of vitamin D are directly involved in the process of fracture repair.

Biochemical and biomechanical properties of avian callus after local administration of dihydroxylated vitamin D metabolites.

In vitamin D-fed chicks 1,25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 were implanted into experimentally-produced fractures of the mid-tibia. The mechanical and biochemical properties of the tibia were evaluated for two weeks, including torsion tests, measurement of alkaline phosphatase activity, 45Ca incorporation, and Ca2+ content. Both dihydroxylated metabolites of vitamin D3 had a direct effect on endochondral bone formation. 24,25(OH)2D3 strengthened the callus, and raised alkaline phosphate activity in the first seven days after fracture. 1,25(OH)2D3 decreased the strength of the callus concomitant with a reduction in 45Ca incorporation. It is suggested that local application of 24,25(OH)2D3 into fractures may accelerate healing and prevent non-union.

Migratory multiple bone involvement in a patient with systemic mastocytosis.

A young patient with severe generalized osteopenia and multiple compressed vertebral fractures caused by systemic mastocytosis is presented. Extensive clinical, laboratory, and pathologic examination showed the involvement of the skeleton alone. Follow-up bone scintigraphy with Tc-99m MDP during a period of 6 years demonstrated migratory multiple axial lesions. These results suggest that Tc-99m MDP imaging is an accurate detection of the activity of the disease.

Centrocentral anastomosis with autologous nerve graft treatment of foot and ankle neuromas.

Painful neuromatas in the foot and around the ankle can be difficult to treat. Five patients of clinically and histologically proven neuromas underwent centrocentral union with autologous transplantation. Three patients had previous toe amputations involving multiple operations. One patient had failed multiple operative treatments for Morton's neuroma in his 3rd web space. One patient had a neuroma in his superficial peroneal nerve caused by a gun shot wound. All patients but one showed definitive subjective and objective improvement after centrocentral union with the interposed autologous nerve graft. The patient with "recurrent" Morton's neuroma had the least improvement. This technique can be recommended as an alternative for the prevention of painful stump neuromata.

Calcitriol increases Ca2+-ATPase activity.

Treatment with calcitriol of isolated cartilage cells derived from epiphyseal growth plates of rachitic chicks results in reduced intracellular calcium concentrations. The reduction in calcium was found to correlate with increased activity of Ca2+-ATPase. The activities of Na+-K+-ATPase and of Mg2+-ATPase did not change in response to the treatment with calcitriol. It is suggested that calcitriol regulates intracellular calcium by modulating the activity of the Ca2+-pumping ATPase.

Parosteal lipoma of the proximal radius: a report of five cases.

Parosteal lipoma of the proximal radius is a benign, slow-growing tumor. It may cause compression of either the posterior interosseous or the superficial branch of the radial nerve. Surgical excision usually leads to complete recovery. Five cases of parosteal lipoma of the proximal radius are presented. X-ray films demonstrated a radiolucent mass in contact with the radius. Two patients had signs of posterior interosseous nerve compression, and two showed signs of superficial radial nerve compression. In one case the lipoma surrounded an exostosis arising from the proximal radius. The tumors were excised in four patients. The three patients with neurologic involvement recovered fully. One patient refused surgery, and posterior interosseous nerve paralysis developed.

Influence of 1,25-hydroxyvitamin D3 on cytosolic free calcium concentrations.

Using isolated cartilage cells from the epiphyseal growth plate of rachitic chicks and utilizing the fluorescence indicator quin2 for measurements of cytosolic free calcium, it has been possible to demonstrate that 1,25-dihydroxyvitamin D3 regulates the concentrations of cytosolic free calcium. The reduction in cytosolic free calcium is associated with inhibition of the activity of alkaline phosphatase. As several hours are required before an effect on cytosolic free calcium can be observed in the cells, it is suggested that the action is dependent on genomic interactions.

Decrease in bone level of 1,25-dihydroxyvitamin D in women over 45 years old.

The most active metabolite of vitamin D is 1,25-dihydroxyvitamin D [1,25(OH)2D]. Its level in the bone may play a role in the pathogenesis of metabolic bone diseases such as osteoporosis. To assess this, and to see whether there is correlation between serum and bone levels, we studied serum and bone samples taken from 43 patients (18 men and 25 women) undergoing different orthopedic procedures. Patients were studied according to sex and age groups (less than 45 years, 46-60 years, greater than 61 years). Serum level of 1,25(OH)2D was found to be 29.7 +/- 2.61 pg/ml (mean +/- SEM) for women, 32.2 +/- 3.86 pg/ml for men, and 30.7 +/- 2.18 pg/ml for the group as a whole. No significant statistical differences were found among age subgroups in either sex or between sexes. Bone level of 1,25(OH)2D was found to be 31.5 +/- 4.46 pg/g for women, 26.5 +/- 3.06 pg/g for men, and 29.4 +/- 2.81 pg/g for the entire group. No significant statistical difference was found between the age subgroups for men. However, the level of 1,25(OH)2D was found to be higher in the group of younger women (less than 45 years) compared with the older women (46-60 years and greater than 61 years) (P less than 0.005).

Proteoglycan synthesis in vitamin D-deficient cartilage: recovery from vitamin D deficiency.

Vitamin D appears to be required for mineralization of skeletal elements. There is also evidence that cartilage proteoglycans may be involved in the regulation of mineralization. Previous studies have shown an alteration in the structure of the proteoglycans of the epiphyseal growth cartilage as a result of the decrease in serum calcium related to deficiency of dietary vitamin D. Vitamin D deficiency also induces a thickening of the epiphyseal growth plate presumably because of the inhibition of maturation of the growth plate chondrocytes. In order to compare the effect on proteoglycan structure with that on growth plate morphology, the proteoglycans of healing epiphyseal cartilage were characterized. The results indicate that, consistent with previous data, in vitamin D-deficient hatching chicks, the proteoglycans of the growth cartilage, but not of the articular cartilage, are smaller in monomer size with slightly smaller chondroitin sulfate chains whose sulfation pattern is unaltered. Sternal cartilage proteoglycans are unaffected. During recovery from vitamin D deficiency, the proteoglycans isolated from the growth cartilage are still not completely normal one day after supplementation with vitamin D, but are indistinguishable from normal by four days. In addition, the results conflict with those of a previous study in which only growth cartilage of hatchling chicks, not sternal or articular cartilage, was reported to synthesize large proteoglycans. Instead, all of these cartilages in the normal chicken have been found in this study to produce large proteoglycans of a size typical for mammalian cartilage and embryonic chick cartilage.

Salmonella paratyphi C osteomyelitis: report of two separate episodes 17 years apart.

Osteomyelitis secondary to salmonella infection is well documented in the literature. Infection in more than one focus has also been described. To the best of our knowledge this is the first report of recurrent osteomyelitis in a normal host (a 35-year-old man) with the same organism (S. paratyphi C) in different sites 17 years apart.

Sarcoidosis masquerading as a parathyroid adenoma.

Two patients presented with a presumptive diagnosis of hyperparathyroidism. Surgically excised "parathyroid glands" were found to be, in fact, large lymph nodes with sarcoid granulomata. In one patient, the preoperative localization of the "parathyroid adenoma" was based on scintigraphy (thallium-technetium subtraction imaging) and sonography procedures. The differential diagnosis of hypercalcemia, and positive scintigraphy-sonography studies, must include sarcoidosis in an isolated cervical lymph nodes.

Management of pyogenic vertebral osteomyelitis with spinal cord compression in the elderly.

Five elderly and debilitated patients presented with compressive myelopathy due to pyogenic spondylitis. All had undergone surgery which consisted of eradication of the infected tissue via an anterior approach followed by primary bone graft. Supplementary antibiotic treatment was determined by intraoperative bacteriological culture. This aggressive approach, disregarding the patients' advanced age and poor general medical state, resulted in total resolution of the neurological deficit and the patients' return to their preoperative everyday activity.

Decrease in bone levels of 1,25-dihydroxyvitamin D in women with subcapital fracture of the femur.

In a previous study we were able to show that in women over the age of 45 the level of 1,25-dihydroxyvitamin D (1,25(OH)2D) in bone, but not in serum, is significantly reduced when compared with younger women. In the present study we measured the concentration of 1,25(OH)2D in sera and bones of 19 female patients with subcapital fractures of the femur, mean age 78 +/- 2 years. We were able to show that serum levels of 1,25(OH)2D were within the normal range, while bone levels were markedly reduced compared to levels in femoral bone obtained from young female cadavers or to the previously reported levels in non-osteoporotic elderly women. Thus, reduced levels of 1,25(OH)2D in bones of elderly women may lead, together with other factors, to subcapital fractures.