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.

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.

Osteoporosis and increased bone fractures in cerebrotendinous xanthomatosis.

Significant osteoporosis determined by skeleton radiography and bone densitometry was found in 15 patients with cerebrotendinous xanthomatosis (CTX) whose mean age was 31 +/- 11 years. In three CTX patients, bone biopsies confirmed osteoporosis. Nine patients also sustained bone fractures following minimal trauma. Serum 25-hydroxyvitamin D ([25-OHD] 14.6 +/- 6.6 ng/mL v [normal] 30.4 +/- 8.0 ng/mL; P < .001) and 24,25-dihydroxyvitamin D ([24,25(OH)2D] 1.2 +/- 0.4 ng/mL v [normal] 2.7 +/- 0.8 ng/mL; P < .001) levels were low. Serum concentrations of 1,25(OH)2D, calcium, inorganic phosphorus, alkaline phosphatase, parathyroid hormone, and calcitonin were normal. Patients showed classic manifestations of CTX, including dementia, pyramidal and cerebellar insufficiency, peripheral neuropathy, cataracts, and tendon xanthomas associated with elevated serum cholestanol concentrations. These results demonstrate that extensive osteoporosis and increased risk of bone fractures are components of this inherited disease.

Thromboxane A2 in postischemic acute compartmental syndrome.

OBJECTIVE: To evaluate whether thromboxane A2 participates in the ischemia-reperfusion injury associated with acute compartmental syndrome (ACS) and if by using a cyclooxygenase inhibitor this can be either reduced or abolished. DESIGN: To assess the role of thromboxane A2 in ACS, a tourniquet was applied for 2 hours to the hind limb of 12 dogs. Group 1 (n = 6) served as controls while group 2 (n = 6) was pretreated with lysine-acetyl-salicylate (Lysoprim). Blood thromboxane B2 levels and intracompartmental pressures were assayed prior to inflation of the tourniquet and at 5 minutes, 90 minutes, and 24, 72, and 144 hours after deflation. RESULTS: Five minutes after deflation, the compartmental pressure increased from 11.2 +/- 2.2 mm Hg to 16.1 +/- 3.3 mm Hg and 17 +/- 2.2 mm Hg (mean +/- SD) in groups 2 and 1, respectively. At 90 minutes and 24 hours, pressures were 17.1 +/- 3.3 mm Hg and 23.2 +/- 3.3 mm Hg (P<.01) and 15.3 +/- 2.6 mm Hg and 25.2 +/- 1.8 mm Hg (mean +/- SD) (P<.001), respectively, in groups 2 and 1. A similar effect, although of a lesser magnitude, was observed in the counterlateral limb. Thromboxane B2 levels increased from a mean (+/- SD) of 46 +/- 5.5 pg/0.1 mL to 132 +/- 7.5 pg/0.1 mL at 90 minutes in group 1, while remaining unchanged in group 2. CONCLUSIONS: Thromboxane A2 plays a major role in the ischemia-reperfusion injury of acute compartmental syndrome. By using a cyclooxygenase inhibitor both the levels of thromboxane and the compartmental pressures can be reduced.

Prostaglandin release by normal and osteomyelitic human bones.

The release of prostaglandin E (PGE) and prostacyclin (as 6-keto PGF1 alpha) by human osteomyelitic bone, compared with normal (control) bone, incubated in vitro was evaluated. Prostacyclin was the main arachidonic acid metabolite released by normal human bone, and similar quantities were released by osteomyelitic bone. However, PGE production was 5-30-fold higher in osteomyelitic bone, compared with control, thus becoming the major prostanoid in this disease. It is concluded that PGE production is probably involved in the inflammatory and/or bone resorption processes that occur in osteomyelitis.

Serum and bone vitamin D metabolites in elective patients and patients after fracture.

Vitamin D metabolite levels were measured in serum and bone samples obtained from 27 patients undergoing elective bony procedures and from 28 patients operated on after a fracture. Serum 25 hydroxyvitamin D3 (25-OH-D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) did not differ significantly between the elective and fracture patients, but serum 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) was significantly reduced in the fracture patients. Very little 25-OH-D3 was found in bone, although it was the major vitamin D metabolite in serum (90%). In elective patients bone levels of 24,25(OH)2D3 and 1,25(OH)2D3 were similar to those in serum; however, in bone from around pertrochanteric fractures, but not from subcapital or patellar fractures, the concentrations of these compounds were considerably increased. These findings may shed light on the mechanism of callus formation and on the role of vitamin D metabolites in bone healing.

The treatment of osteomyelitis of the tibia with sodium salicylate. An experimental study in rabbits.

Osteomyelitis was induced in the tibiae of rabbits by injecting a suspension of Staphylococcus aureus and sodium tetradecylsulphate, a sclerosing agent. These rabbits were then divided into two groups: one group remained untreated and the other was fed a diet containing sodium salicylate. Two and four weeks after induction of osteomyelitis the tibiae taken from untreated rabbits with osteomyelitis and incubated in vitro released significantly more prostaglandin E and F than the control uninjected or uninfected tibiae. Tibiae taken from rabbits treated with sodium salicylate showed minimal radiographic changes and a significantly decreased release of prostaglandin E and F compared to the untreated rabbits. Prostaglandins are known to be potent bone resorbing agents and the results of this study suggest that they may also be involved in the destruction of bone which is characteristic of osteomyelitis. The treatment of rabbits with osteomyelitis using anti-inflammatory drugs, which block synthesis of prostaglandins, in addition to antibiotics, may prevent the destruction of bone and possible sequestration thereby decreasing the risk of chronic disease.

Release of prostaglandins from bone and muscle after tibial fracture. An experimental study in rabbits.

The release of prostaglandins E and F from the tibiae of rabbits and the surrounding muscle in vitro after fracture and pinning, or pinning alone, has been compared to the release from unoperated tissues. The fractured tibiae released significantly more prostaglandins E and F than the control tibiae three to 14 days after operation. The pinned tibiae also released more of the two prostaglandins, although this was significant only after 14 days. Consequently it was only around the third day that the fractured tibiae released significantly more prostaglandin E than the tibiae which had been pinned, but not fractured. Similar results were obtained for the release from the muscles surrounding the tibiae. Prostaglandins are important mediators of inflammation as well as potent stimulators of bone resorption. Their increased formation in response to fracture and pinning may stimulate the vascular changes, bone resorption and the proliferation of osteogenic cells observed after trauma to bone.

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.

Patterns of weight distribution under the metatarsal heads.

The longitudinal arch between the heel and the forefoot and the transverse arch between the first and fifth metatarsal heads, absorb shock, energy and force. A device to measure plantar pressure was used in 66 normal healthy subjects and in 294 patients with various types of foot disorder. Only 22 (3%) of a total of 720 feet, had a dynamic metatarsal arch during the stance phase of walking, and all had known abnormality. Our findings show that there is no distal transverse metatarsal arch during the stance phase. This is important for the classification and description of disorders of the foot.

Percutaneous release of trigger digits.

Twenty nine patients with 31 trigger digits were treated by percutaneous release under local anaesthesia using an 18 gauge needle. One patient was lost to follow up, and the remainder were examined at a mean follow-up of 14 months. One patient (one thumb) experienced recurrent symptoms, and required an open release. The remaining 27 patients with 29 trigger digits had complete relief of their symptoms.

Dynamic pressures on the diabetic foot.

A retrospective study was conducted in order to investigate the relation between increased plantar pressure and ulcers in the diabetic foot and contribute more information on this subject. Maximal plantar pressure (MPP) is reported on various areas of the plantar aspects of the feet in 328 diabetic patients and 75 healthy subjects. An increase in MPP under all plantar areas except for the heels was found to be related with increasing severity of the diabetes symptoms. There was also a significant decrease in the application of high pressures to the heels, the metatarsal heads II-IV and the toes.

Compartmental syndrome due to high velocity missile injury of the calf: use of immediate mesh skin grafting.

Two patients with high velocity missile injury to the soft tissues of the calf without major fractures are presented. Both of them developed compartmental syndrome and were treated by debridement, fasciotomy, and immediate mesh split thickness skin graft. The mechanisms of such injury and the advantage of immediate skin grafting are discussed.

'Epiphyseal dysgenesis' in Laurence-Moon-Biedl-Bardet syndrome.

Ten patients with Laurence-Moon-Biedl-Bardet syndrome were investigated. They all belonged to one large family within which several intermarriages had taken place. We found that, apart from the already described abnormalities, these patients suffered from dysgenesis of the following epiphyses: vertebrae, proximal femur, proximal tibia, capitellum, tarsal navicular, and the distal epiphysis of the first metatarsal. The degree of polydactyly, a prominent feature of this syndrome, varied from patient to patient, ranging from a wide fifth metatarsal or metacarpal to a complete sixth digit. As in other epiphyseal dysgenesis, a pseudoepiphysis of the distal first metacarpal was present. One patient (the eldest) was tetraparetic due to severe spinal stenosis.

The use of three-dimensional computed tomography in evaluating snapping scapula syndrome.

This article evaluates imaging of the scapula and scapulothoracic joint in patients with snapping scapula syndrome. Between 1990 and 1996, a total of 20 patients (10 men and 10 women) with snapping scapula syndrome were evaluated. Diagnosis was based on patient complaints and physical examination findings. There were 26 affected scapulae (6 patients had bilateral presentation). Imaging of the scapula included plain radiography, computed tomography (CT), and 3-dimensional computed tomography (3-D CT) reconstruction. Plain radiography revealed bony incongruity between the anterior aspect of the scapula and the chest wall in 7 scapulae, CT revealed such incongruity in 19 scapulae, and 3-D CT revealed incongruity in all 26 scapulae. Treatment was conservative, consisting of nonsteroidal anti-inflammatory drugs, a physiotherapy program, and subscapular injection of a local anesthetic and steroids. In 5 patients who responded poorly to conservative treatment, the region responsible for the snapping was resected. Pain relief and resolution of the snapping were complete following surgery in 4 patients, while pain and crepitation persisted in the fifth. Three-dimensional CT is recommended as the main imaging modality in the evaluation of any patient with snapping scapula syndrome who is a candidate for surgical intervention.

[Treatment of fractures of the femoral neck by primary femoral prosthesis (author's transl)]. / Les fractures du col du fémur. Traitement par prothèse fémorale d'emblée.

The authors have reviewed 230 case of fractures of the femoral neck treated by primary femoral prosthesis. The mortality was 12,6 p. 100 during the first three post operative months, and 16,5 p. 100 after three additional months. The infection rate was 13,9 p. 100, 4,7 p. 100 of the cases being severely infected. The postero lateral approach was more favourable than the antero-lateral approach. Late results were studied on 142 cases. The average follow-up was 4 years. The clinical results were closely dependent on the radiological appearance. When the prosthesis progressively penetrated into the femoral medullary canal incapacitating pain was always present. It is concluded that the use of cement may improve the results in a number of cases.

[Physical 3-dimensional testing of the lumbar spine using the IsoStation B-200].

Low-back pain is not only one of the major medical problems, but the most common. Up to 80% of the population is expected to experience back pain at least once in their lifetime. The functional disability caused by LBP has a major influence on quality of life, as well as its economic aspects. Psychological and social factors are highly involved with LBP. Therefore any advance in objective assessment of LBP is of major importance. We present a relatively new system used for the past 2 years by our departments, the IsoStation B-200 (Isotechnologies Co., NC). This system enables simultaneous 3-D measurements of range of motion, speed of movement and torques in the lumbar back in a highly accurate and reproducible manner. The results are used to classify the status of LBP in terms of severity and disability. They enable us to assess quality of performance and to detect the "symptom magnification syndrome" (SMS), patients with non-physiologic complaints and behavior. We describe in detail the measurement protocol and the exact definitions and criteria used in the process of patient classification. Finally we present the results of our first 238 patients tested. A highly significant difference in almost all measured and calculated parameters was found between the patients with physiologic behavior and those with SMS or nonphysiological behavior. Findings related to all classifications are presented.

Levator scapulae syndrome: an anatomic-clinical study.

Twenty-two patients, all young females, presenting with a common clinical picture of pain over the upper medial angle of the scapula were studied. The dominant shoulder was the most commonly involved (82%). Pain radiated to the neck and shoulder, but rarely to the arm. Movements that stretched the levator scapulae on the affected side aggravated symptoms. Radiographs and bone scans of the shoulders and cervical spine were negative. Increased heat emission from the upper medial angle of the affected shoulder was found on thermography in more than 60% of the patients. Anatomic dissections of 30 cadaveric shoulders showed great variability in the insertion of the levator. A bursa was found between the scapula, the serratus, and the levator in more than 50% of the shoulders. This study suggests that this syndrome, leading to bursitis and pain, may be caused by anatomic variations of the insertion of the levator scapulae and origin of the serratus anterior. This may explain the constant trigger point and crepitation as well as the increased heat emission found on thermography. Local steroid injections relieved symptoms partially in 75% of those patients who underwent treatment.

The release of cytotoxic drugs from acrylic bone cement.

The ability of cis-platinum, 5-fluorouracil, and methotrexate to leach out from various types of bone cements was examined in three different experimental systems: (1) in vitro release in physiological solution; (2) in vitro release in the presence of mouse fibrosarcoma cells; and (3) in vivo release in rabbits. The amount of drugs released was measured either spectrophotometrically by atomic absorption or by using tritium-labeled drugs. In vitro cement pellets were found to release these drugs slowly for up to six months; release was greater in the first few days, rapidly declining with time. Up to 6% of the methotrexate implanted leached out during the entire experiment. The figures for cis-platinum and 5-fluorouracil were much less: 3.3% and 3.4%, respectively. Palacos bone cement had the best leaching properties. The drugs leached out were also effective in reducing the numbers of viable mouse fibrosarcoma cells in tissue culture. In vivo, high levels of the drugs were recovered from blood drained from the operative wound of the rabbits, while very low levels of these drugs were found in the serum. Anticancer drug-loaded cement may be used effectively in the treatment of pathologic fractures and tumor surgery. This delivery method may reduce the side effects that result from systemic administration of such drugs.