A rodent model of HIV protease inhibitor indinavir induced peripheral neuropathy.

HIV-associated sensory neuropathy (HIV-SN) is the most frequent manifestation of HIV disease. It often presents with significant neuropathic pain and is associated with previous exposure to neurotoxic nucleoside reverse transcriptase inhibitors. However, HIV-SN prevalence remains high even in resource-rich settings where these drugs are no longer used. Previous evidence suggests that exposure to indinavir, a protease inhibitor commonly used in antiretroviral therapy, may link to elevated HIV-SN risk. Here, we investigated whether indinavir treatment was associated with the development of a "dying back" axonal neuropathy and changes in pain-relevant limb withdrawal and thigmotactic behaviours. After 2 intravenous injections of indinavir (50 mg/kg, 4 days apart), adult rats developed hind paw mechanical hypersensitivity, which peaked around 2 weeks post first injection (44% reduction from baseline). At this time, animals also had (1) significantly changed thigmotactic behaviour (62% reduction in central zone entries) comparing with the controls and (2) a significant reduction (45%) in hind paw intraepidermal nerve fibre density. Treatment with gabapentin, but not amitriptyline, was associated with a complete attenuation of hind paw mechanical hypersensitivity observed with indinavir treatment. Furthermore, we found a small but significant increase in microglia with the effector morphology in the lumbar spinal dorsal horn in indinavir-treated animals, coupled with significantly increased expression of phospho-p38 in microglia. In summary, we have reported neuropathic pain-related sensory and behavioural changes accompanied by a significant loss of hind paw skin sensory innervation in a rat model of indinavir-induced peripheral neuropathy that is suitable for further pathophysiological investigation and preclinical evaluation of novel analgesics.

Metastasis of renal cancer to the wrist and hand: a case report.

Metastases to the hand and wrist are rare. The lung, breast and kidneys are the most common sites of primary lesions that metastasize in the hand. Phalanges are more commonly involved than metacarpals and wrist. We report the case of a neglected, large metastatic tumour involving a patient's left wrist and metacarpus originating form renal adenocarcinoma cancer, which appeared 2 years prior to the diagnosis of the primary neoplasm. The tumour was resected, but without oncologic margins. After obtaining histological veri- 􀏐ication (clear cell renal cell carcinoma) the patient had been proposed amputation, but he refused and was given chemotherapy. Imaging towards possible other distant metastases (CT and PET scanning) was negative. At 6 months follow -up the patient showed good general condition, no local recurrence, and regained some hand function.

Effect of Clostridium botulinum toxin type A injections into the deep digital flexor muscle on the range of motion of the metacarpus and carpus, and the force distribution underneath the hooves, of sound horses at the walk.

In the treatment of laminitis, reducing deep digital flexor muscle (DDFM) activity might diminish its pull on the distal phalanx, thereby preventing displacement and providing pain relief. Injection of Clostridium botulinum toxin type A into the DDFM of horses is potentially therapeutic. However, the effects of C. botulinum toxin type A on the gait characteristics of sound horses at the walk are not known. The aim of this study was to test if a reduced DDFM activity would lead to (1) alterations of the sagittal range of motion of the metacarpus (SROM) and range of motion of the carpal joint (CROM); (2) changes in the force distribution underneath the hoof (toe vs. heel region: balance index); and (3) changes in the force distribution between the treated and untreated limb (symmetry index). The DDFMs of the left forelimbs of seven sound Royal Dutch Sport Horses were injected with 200 IU C. botulinum toxin type A using electromyography and ultrasound guidance. Measurements using an inertial sensor system and dynamically calibrated pressure plate were performed before and after injections. The SROM and CROM of the treated limb were significantly increased after C. botulinum toxin type A injections. No significant changes were detected in the balance index or in the symmetry index, indicating that no lameness was induced. C. botulinum toxin type A injections into the DDFM of sound horses do not appear to result in substantial gait alterations at the walk.

Inflammatory pain in the rabbit: a new, efficient method for measuring mechanical hyperalgesia in the hind paw.

The discovery of novel analgesic compounds that target some receptors can be challenging due to species differences in ligand pharmacology. If a putative analgesic compound has markedly lower affinity for rodent versus other mammalian orthologs of a receptor, the evaluation of antinociceptive efficacy in non-rodent species becomes necessary. Here, we describe a new, efficient method for measuring inflammation-associated nociception in conscious rabbits. An electronic von Frey device is used, consisting of a rigid plastic tip connected to a force transducer in a hand-held probe. The plastic tip is applied to the plantar surface of a hind paw with increasing force until a withdrawal response is observed. The maximum force (g) tolerated by the rabbit (i.e., withdrawal threshold) is recorded. In young, conscious rabbits (500-700 g), baseline hind paw withdrawal thresholds typically fell within the 60-80 g range. Three hours after injection of the inflammatory agent carrageenan (3%, 200 microL, intra-plantar), withdrawal thresholds dropped by approximately 30-40 g, indicating the presence of punctate mechanical hyperalgesia. The development of hyperalgesia was dose dependently prevented by the NSAID indomethacin (ED50=2.56 mg/kg, p.o.) or the bradykinin B2 receptor peptide antagonist HOE 140 (intra-paw administration). An established hyperalgesia was dose dependently reversed by morphine sulfate (ED50=0.096 mg/kg, s.c.) or the bradykinin B1 receptor peptide antagonist [des-Arg10, Leu9]-kallidin (ED50=0.45 mg/kg, s.c.). Rabbits treated with the novel B(1) receptor small molecule antagonist compound A also showed dose-dependent reversal of hyperalgesia (ED50=20.19 mg/kg, s.c.) and analysis of plasma samples taken from these rabbits showed that, unlike other rabbit pain models, the current method permits the evaluation of pharmacokinetic-pharmacodynamic (PK-PD) relationships (compound A plasma EC50=402.6 nM). We conclude that the Electrovonfrey method can be used in rabbits with inflammatory pain to generate reliable dose- and plasma concentration-effect curves for different classes of analgesics.

Preliminary study on the effect of parenteral naloxone, alone and in association with calcium gluconate, on bone healing in an ovine "drill hole" model system.

BACKGROUND: Several diseases affect bone healing and physiology. Many drugs that are commonly used in orthopaedics as "analgesics" or anti-inflammatory agents impair bone healing. Stressful conditions are associated with decreased serum osteocalcin concentration. High endorphin levels alter calcium metabolism, blocking the membrane channels by which calcium normally enters cells. The consequent decrease of intracellular calcium impairs the activities of calcium-related enzymes. Naloxone is a pure opioid antagonist. Morphine-induced osteocalcin inhibition was abolished when osteoblasts were incubated with naloxone. Naloxone restored the altered cellular and tissue physiology by removing beta-endorphins from specific receptors. However, this is only possible if the circulating Ca concentration is adequate. The aim of the present study was to evaluate the efficacy of parenteral naloxone administration in inducing fast mineralization and callus remodelling in a group of sheep with a standardised bone lesion. METHODS: Twenty ewes were randomly assigned to 4 treatment groups. Group A acted as control, group B received a solution of calcium gluconate, group C a solution of naloxone, and group D a solution of calcium gluconate and naloxone. A transverse hole was drilled in the left metacarpus, including both cortices, then parenteral treatment was administered intramuscularly, daily for four weeks. Healing was evaluated by weekly radiographic examination for eight weeks. For quantitative evaluation, the ratio of the radiographic bone density between the drill area and the adjacent cortical bone was calculated. After eight weeks the sheep were slaughtered and a sample of bone was collected for histopathology RESULTS: Group D showed a higher radiographic ratio than the other groups. Sheep not treated with naloxone showed a persistently lower ratio in the lateral than the medial cortex (P < 0.01). Histopathology of bone samples showed more caverns and fewer osteoblasts in group D than in the other groups (P

[Clinical trial for differentiation between corticoid-induced osteoporosis and periarticular demineralization via digital radiogrammetry in patients suffering from rheumatoid arthritis]. / Versuch der Differenzierung zwischen kortikoidinduzierter Osteopenie und periartikulärer Demineralisation mit Hilfe der Digitalen Radiogrammetrie (DXR) bei Patienten mit rheumatoider Arthritis.

PURPOSE: To investigate a new bone densitometric technology based on digital radiogrammetry (DXR) with respect to its ability to measure severity-dependent variations of bone mineral density (BMD) in patients with rheumatoid arthritis and to differentiate between corticoid-induced and periarticular bone mineral density loss. PATIENTS AND METHODS: A total of 153 randomly selected patients suffering from verified rheumatoid arthritis underwent digitally performed plain radiographs of the non-dominant hand and also measurements of dual-energy X-ray absorptiometry (DXA) regarding total femur and lumbar spine in 102 patients and peripheral quantitative computed tomography (pQCT) regarding the distal radius in 51 patients. Using DXR the radiographs of the non-dominant hand were analyzed for cortical bone mineral density calculation. The severity was classified in the DXA group using the Ratingen score. Furthermore, both study populations were divided into patients with and without corticoid therapy. RESULTS: Correlations between BMD determined by DXR and by DXA (R=0.44 for lumbar spine and R=0.61 for total femur) versus pQCT (0.46

Effects of alendronate on metacarpal and lumbar bone mineral density, bone resorption, and chronic back pain in postmenopausal women with osteoporosis.

The purpose of this study was to investigate the effect of alendronate on metacarpal and lumbar bone mineral density (BMD), bone resorption, and chronic back pain in postmenopausal women with osteoporosis. Eighty postmenopausal women with osteoporosis, 59-88 years of age, were divided into two groups of 40 each according to the site of BMD measurement: the metacarpus (M) and the lumbar spine (L). All of them were treated with alendronate (5 mg/day) for 12 months. Metacarpal or lumbar BMD was measured by computed X-ray densitometry or dual-energy X-ray absorptiometry in the M or the L group, respectively, at baseline and every 6 months. Urinary cross-linked N-terminal telopeptides of type I collagen (NTX) were measured by enzyme-linked immunosorbent assay, and chronic back pain was evaluated by face scale score at baseline and every 6 months in both groups. There were no significant differences in baseline characteristics, including age, body mass index, years since menopause, urinary NTX level, face scale score, or number of prevalent vertebral fractures per patient between the two groups. Urinary NTX level was reduced and chronic back pain was improved similarly in both groups. Whereas metacarpal BMD did not significantly change in the M group (0.20% increase), lumbar BMD increased by 8.15% in the L group. These results suggest that although alendronate increases BMD of the lumbar spine, which is rich in cancellous bone, and improves chronic back pain, with suppression of bone resorption in postmenopausal women with osteoporosis, it may fail to increase cortical BMD of the metacarpus, a distal site of the upper extremity.

Effect of perineural anesthesia on the ultrasonographic appearance of equine palmar metacarpal structures.

The purpose of this study was to describe ultrasonographic changes of the equine palmar metacarpal area attributed to the infiltration of local anesthetic solution and to determine whether these changes were noted immediately or at 24 h. The palmar metacarpal region of one forelimb in each of six horses was examined ultrasonographically with a 10-MHz linear array transducer and a 7.5-MHz curvilinear transducer. Transverse and longitudinal images were recorded at 5-cm intervals distal to the accessory carpal bone. High and low palmar and palmar metacarpal nerve blocks were performed with a 2% mepivacaine hydrochloride solution. Ultrasonographic examinations similar to the initial examination then were performed immediately, 1 h and 24 h postinjection. Cross-sectional area and mean pixel value were determined for the superficial and deep digital flexor tendons, the accessory ligament of the deep digital flexor tendon, the suspensory ligament, and the suspensory branches at each level and time period. Subjective ultrasonographic changes also were noted. No significant difference was noted in the cross-sectional area or mean pixel value of any structure at any level or time period compared to baseline. Subjective changes in the tendons and ligaments were not noted. There was mild hypoechoic swelling of the surrounding soft tissues and gas in the region of the injections. Gas could interfere with the evaluation of the origin of the suspensory ligament and the proximal portion of the accessory ligament of the deep digital flexor tendon within the first hour but was not detectable ultrasonographically at 24 h. Based on these findings, if gas interferes with an ultrasonographic examination performed temporally close to perineural anesthesia, a repeat examination at 24 h is recommended.

[Steroid-induced osteonecrosis of femoral condyles and bilateral Freyberg's disease]. / Kortisoninduzierte Osteonekrose der Femurkondylen und Morbus Freyberg beidseits.

We report on a patient with steroid-induced osteonecrosis of the femoral condyles after therapy of an acute lymphatic leukemia. Because of continuing bilateral knee pain, we performed osteochondral autografting of the right femoral condyle in two steps. During the follow-up period, the patient developed bilateral Freyberg's disease, which was also successfully treated by surgery. The MRIs which we performed as a follow-up 3 years later showed complete incorporation and vitality of the transplanted cylinders. No further clinical symptoms occurred.

Bone mineral density in Turner syndrome: relation to GH treatment and estrogen treatment.

The bone mineral density (BMD) of the second metacarpal bone of the left hand was measured in 57 patients with Turner syndrome by the digital image processing (DIP) method to study the relations between the treatment regimen and their bone mineral density. BMD SD score in the patients who had started the GH treatment before 10 years old was within +/-2SD of the standard before 14 years, but the score decreased to below -2SD after 14 years. In the patients who had started GH treatment after 10 years old, BMD score were significantly lower than -2SD, although there was tendency to increased. In the patients who had estrogen after 15 years old, BMD did not increase with GH alone and slowly increased after estrogen replacement. In the other two patients who had started sex steroid hormone replacement treatment before 15 years old, BMD maintained +/-2SD. In patients who received combined GH and LH-RH analog treatment, their BMD score did not increase during LH-RH analog treatment. It slowly increased but was still below -3SD after stop of LH-RH analog and start of estrogen treatment. In Turner syndrome, GH may play a role in maintaining prepubertal BMD levels [4], and estrogen plays an important role in pubertal BMD increment. It is recommended that estrogen treatment is started before 15 years of age for maintenance of normal BMD level.

Influence of multiple injections of vitamin E on intramuscular collagen and bone characteristics in suckling lambs.

We studied the influence of vitamin E on intramuscular collagen characteristics and on metacarpal growth plate evolution in suckling lambs. Twenty-four 5-d-old Ile de France suckling male lambs were divided into four equal weight groups, and weekly i.m. injections of DL-alpha-tocopheryl acetate (Control group, 0 IU; Group 1, 625 IU; Group 2, 1,000 IU; and Group 3, 1,500 IU) were given until the lambs were 33 d old. Blood samples were withdrawn for plasma alpha-tocopherol, cholesterol, and triglyceride analyses when the lambs were slaughtered at 40 d of age. Hot carcass weight, metacarpal and metatarsal bone characteristics, and metacarpal growth plate width were measured. After 24 h at 2 to 4 degrees C, semitendinosus muscles were removed for intramuscular collagen analyses. Weight was not influenced by treatment, but lambs in Group 1 had a higher (P < .01) intramuscular collagen content than the other groups. A positive quadratic correlation was found between total collagen and vitamin E doses (r = .511; P < .05). Amount and percentage of soluble collagen increased in muscles of all three vitamin E-treated groups compared with the control group. However, hydroxylysyl pyridinoline concentration decreased with vitamin E injection, but the difference compared to control lambs was only significant for the group injected with 1,000 IU. Amount of soluble collagen was strongly correlated to total collagen concentration (r = .879; P < .0001). It was also related to the alpha-tocopherol/(cholesterol + triglycerides) ratio in plasma (r = .431; P < .04). However, the correlation between soluble collagen percentage and alpha-tocopherol concentration in plasma was not significant (r = .369; P < .08). Bone length, weight, and diameter did not change, but the thickness of metacarpal growth plate increased as the DL-alpha-tocopheryl acetate dose increased; in Groups 2 and 3, the growth plate was significantly wider than in Group 1 and the controls. Growth plate width correlated with alpha-tocopherol/(cholesterol + triglycerides) ratio in plasma (r = .481; P < .02).

Decreased bone resorption, osteoclast differentiation, and expression of vacuolar H+-ATPase in antisense DNA-treated mouse metacarpal and calvaria cultures ex vivo.

Expression and function of vacuolar H(+)-ATPase, a key enzyme in bone resorption, were monitored in antisense DNA-treated bone organ cultures ex vivo. A novel fluoroimmunoassay was used to quantitate mRNA levels after treatment with various antisense, sense, or random DNA oligonucleotides. Conventional slot blots and in vitro translation experiments were used to monitor the efficiency of the antisense molecules. In cell cultures, the used antisense molecules were transported into osteoclasts and a population of mononuclear cells. A significant decrease in bone resorption and in the expression of the 16 kDa, 31 kDa, 42 kDa, 60 kDa, 70 kDa, and 116 kDa subunits of V-ATPase was seen after antisense treatment. Also, osteoclast differentiation was decreased in antisense-treated mouse metacarpal cultures. These data show that the proper function of V-ATPase in osteoclasts requires expression of the 16 kDa, 31 kDa, 42 kDa, 60 kDa, 70 kDa, and 116 kDa subunits of V-ATPase. Antisense DNA molecules can be used to inhibit osteoclast differentiation and function in tissue cultures, in which the physical and chemical cellular environment resembles that in vivo. However, more studies are needed to learn if antisense DNA molecules can be used for inhibiting bone resorption also in vivo.

Menatetrenone ameliorates osteopenia in disuse-affected limbs of vitamin D- and K-deficient stroke patients.

Significant reduction in bone mineral density (BMD) occurs in stroke patients on the hemiplegic and contralateral sides, correlating with the degree of paralysis and vitamin D and K deficiency due to malnutrition, and increasing the risk of hip fracture. We evaluated the efficacy of vitamin K2 (menatetrenone: menaquinone-4; MK-4) in maintaining BMD by comparing serum biochemical indices of bone metabolism between treated and untreated patients. In a random and prospective study, of 108 hemiplegic patients following stroke, 54 received 45 mg menatetrenone daily (MK-4 group, n = 54) for 12 months, and the remaining 54 (untreatment group) did not. Nine patients excluded from the study. The BMD in the second metacarpals and serum indices of bone metabolism were determined. BMD on the hemiplegic side increased by 4.3% in the MK-4 group and decreased by 4.7% in the untreated group (p < 0.0001), while BMD on the intact side decreased by 0.9% in the MK-4 group and by 2.7% in the untreated group (p < 0.0001). At baseline, patients of both groups showed vitamin D and K1 deficiencies, high serum levels of ionized calcium, pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), and low levels of parathyroid hormones (PTH) and bone Gla proteins (BGP), indicating that immobilization-induced hypercalcemia inhibits renal synthesis of 1, 25-dihydroxyvitamin D (1, 25-[OH]2D) and compensatory PTH secretion. Both vitamins K1 and K2 increased by 97.6% and 666.9%, respectively, in the MK-4 group. Correspondingly, a significant increase in BGP and decreases in both ICTP and calcium were observed in the MK-4 group, in association with a simultaneous increase in both PTH and 1, 25-[OH]2D. One patient in the untreated group suffered from a hip fracture, compared with none in the MK-4 group. The treatment with MK-4 can increase the BMD of disused and vitamin D- and K-deficient hemiplegic bone by increasing the vitamin K concentration, and it also can decrease calcium levels through inhibition of bone resorption, resulting in an increase in 1, 25-[OH]2D concentration.

Complementary medical treatment for Colles' fracture: a comparative, randomized, longitudinal study.

In 45 women with Colles' fracture, two types of complementary medical treatment (calcitonin with calcium [SCT+Ca] and calcium alone [Ca]) were compared with placebo. Consecutive patients were assigned randomly to one of the three study groups at the time of inclusion in the study: 15 women (68.6 +/- 5.7 years) were given 100 IU/day I.M. of SCT plus 1200 mg of elemental Ca for 10 successive days each month; 15 women (71.7 +/- 6.1 years) were given only 1200 mg of elemental Ca for 10 days each month; and 15 women (66.9 +/- 7. 9 years) were treated with placebo. Biochemical and radiogrammetric studies were made at baseline and after 1 year of treatment. In the SCT+Ca group tartrate-resistant acid phosphatase decreased (Wilcoxon test, P = 0.014) and the metacarpal index and the cortical and total area (CA/TA) ratio increased (both P = 0.001). In the group treated with Ca alone, no changes were observed. In the placebo group, the metacarpal index and CA/TA decreased (P = 0.015 and P = 0.007, respectively). Ca alone, at the dosage used here, inhibited bone loss after Colles' fracture. The addition of SCT to Ca administration not only impeded bone loss but significantly increased cortical bone mass.

Amelioration of hemiplegia-associated osteopenia more than 4 years after stroke by 1 alpha-hydroxyvitamin D3 and calcium supplementation.

BACKGROUND AND PURPOSE: It has been demonstrated that bone mass was significantly reduced on the hemiplegic side of stroke patients, which might increase their risk of hip fracture. We evaluated the efficacy of 1 alpha-hydroxyvitamin D3 [1 alpha (OH)D3] and supplemental elemental calcium in maintaining bone mass and decreasing the incidence of hip fractures after hemiplegic stroke. METHODS: In a randomized study, 64 patients with hemiplegia after stroke with a mean duration of illness of 4.8 years received either 1 microgram 1 alpha (OH)D3 daily (treatment group, n = 30) or an inactive placebo (placebo group, n = 34) for 6 months and were observed for this duration. Both groups received 300 mg of elemental calcium daily. The bone mineral density (BMD) and metacarpal index (MCI) in the second metacarpals were determined by computed x-ray densitometry. The incidence of hip fractures in these patients was recorded. RESULTS: BMD on the hemiplegic side decreased by 2.4% in the treatment group and 8.9% in the placebo group (P = .0021), while BMD on the intact side increased by 3.5% and decreased by 6.3% in the treated and placebo groups, respectively (P = .0177). In the treatment group, the difference in BMD between hemiplegic and nonhemiplegic sides decreased significantly compared with that before randomization. This difference increased in the placebo group. We observed a similar improvement in MCI in the treatment group but not in the placebo group. Four patients in the placebo group suffered a hip fracture compared with none in the treatment group (P = .0362). CONCLUSIONS: Treatment with 1 alpha (OH)D3 and supplemental elemental calcium can reduce the risk of hip fractures and can prevent further decreases in BMD and MCI on the hemiplegic side of patients with a long-standing stroke. Treatment also may improve these indices on the intact side.

Ultrasonic assessment of calcaneus in inhabitants in a cadmium-polluted area.

We used ultrasound (US) transmission to evaluate the speed of sound (SOS) and broadband ultrasonic attenuation (BUA) in the calcaneus in 17 male and 18 female inhabitants of a Cd-polluted area and 23 men and 45 women living in a nonpolluted area. Significant decreases in SOS and stiffness (Stiff), which was an index empirically derived from SOS and BUA, were found in Cd-exposed women. To evaluate the usefulness of the US measurements for detecting bone abnormality in Cd-exposed people, we examined the associations with the bone measurements of metacarpus by the previously used microdensitometry (MD) method and the grade of renal tubular damage due to Cd exposure. Bone density estimated by MD, sigmaGS/D, was significantly correlated with BUA, SOS, and Stiff in the Cd-exposed men and with BUA and Stiff in the Cd-exposed women. Further, in the Cd-exposed women, the decreases in BUA and Stiff correlated significantly with the increases in urinary beta 2-microglobulin, while sigmaGS/D by the MD method did not. These results suggest that the measurement of the calcaneus using US is not only radiation free but also can be used as a tool for population surveys aiming to evaluate bone damage in people, especially women, showing renal tubular damage due to environmental Cd exposure.

Energy-dispersive X-ray microanalysis of calcified tissues after NaOCl treatment and/or resin embedding.

By energy-dispersive X-ray microanalysis (EDX) in scanning electron microscopy, we studied the calcification of the inner-basic lamellas of a cow bone and the coronal cementum of a horse tooth treated with sodium hypochlorite (NaOCl). These tissues were divided into 4 groups with a combination of NaOCl treatment and polyester-resin embedding including, [A]: non-NaOCl + Resin, [B]: non-NaOCl + non-resin, [C]: NaOCl + Resin, and [D]: NaOCl + non-Resin. From the Ca and P values by EDX analysis, it was suggested that the natural porous spaces of [B] were higher than those of [A], and both the natural and NaOCl-soluble porous spaces were highest in [D]. However, [A] had the lowest porous spaces in both the tissues because the micropores formed 3-dimensionally by NaOCl treatment might be incompletely filled with the resin. The backscattered electron microscopy and the difference of the Ca/P ratios indicated that the NaOCl treatment of the calcified tissues caused some minerals besides organic materials to dissolve. Thus, the sample preparation of [B] is suitable for the quantitative EDX of calcified tissues, whereas the data of [C] except for the Ca/P ratio may be used to approximate the Ca and P contents.

Effects of experimental conditions on the release of 45calcium from prelabeled fetal mouse long bones.

Embryonic/neonatal bones in culture are commonly used for the study of osteoclastic resorption in vitro. For this purpose, the release of 45calcium (45Ca) from prelabeled bones is measured as an index of resorption. We studied 45Ca release from two types of long bone explants after different preparation methods: 17-day-old fetal mouse radii/ulnae with and without cartilage ends (intact radii/ulnae and shafts, respectively), and intact 18-day old metacarpals/metatarsals. In addition, we examined the effect of different culture conditions, such as cultures performed under the surface of the medium or at the interphase of medium and air, on 45Ca release and histology. When intact radii/ulnae were cultured under the surface of the medium, there was always a significant amount (10%) of net basal 45Ca release (corrected for physicochemical exchange) that was not due to osteoclastic resorption, as it could not be suppressed by inhibitors of resorption even at high concentrations. Moreover, histologically TRAcP-positive cells were almost absent after culture and the bone marrow/stromal cells in the center of the bone appeared necrotic, possibly due to a lack of oxygen. Under these culture conditions, osteoclasts could survive in shafts as well as in PTH-stimulated intact radii/ulnae, but a constant amount of 10% 45Ca, not due to resorption, was still released in the medium. When these explants were cultured at the interphase of medium and air, basal and stimulated 45Ca release originated from osteoclastic resorption. In contrast, in 18-day-old fetal mouse metacarpals/metatarsals, the experimental conditions applied did not affect 45Ca release, which was always due to resorption of the explants by osteoclasts.(ABSTRACT TRUNCATED AT 250 WORDS)

Total and regional bone mineral content and fracture rate in postmenopausal osteoporosis treated with salmon calcitonin: a prospective study.

Seventy-two postmenopausal osteoporotic women having more than one nontraumatic vertebral crush fracture were studied. Thirty-six of them, aged 68.8 +/- 1.2 years (18 +/- 4 YSM-years since menopause), were treated with 100 IU/day of salmon calcitonin i.m. plus 500 mg of elemental calcium for 10 days each month. The remaining 36 patients, aged 69.6 +/- 1.4 years (19 +/- 3 YSM), were given only 500 mg of elemental calcium for 10 days each month. All patients underwent clinical and analytical evaluation every 3 months. Radiological evaluation, assessment of vertebral deformities, and metacarpal radiogrammetry were done every 6 months. Densitometric measurements of total and regional bone mass were made every 12 months. At 24 months, the calcitonin group showed a 60% reduction in the number of new fractures and the group receiving only calcium had a 45% increase (P < 0.001). The incidence of vertebral fractures was 0.07 per patient-year in the group treated with calcitonin and 0.45 per patient-year in the group treated with calcium (P < 0.001). At 2 years, the calcitonin group showed a 12% increase in cortical bone mass on metacarpal radiogrammetry, a 16% increase in the axial skeleton on trunk densitometry, a 3.5% increase in total body bone mineral content, a 30.7% increase in pelvic bone mineral content, and a 6.2% increase in arm bone mineral content (all P < 0.001). In the group treated with calcium alone there was a loss of bone mass in every region. These findings suggest that salmon calcitonin is effective in the treatment of osteoporosis and show that it acts on cortical and trabecular bone.

Influence of incremental zeranol implant doses on the chemical and physical characteristics of third metacarpal bone and chemical composition of liver and soft tissue from feedlot steers.

Chemical and physical characteristics of third metacarpal bones and liver and rib soft tissue composition from feedlot steers were determined. Steers were selected (32 from each experimental location) to represent the range in slaughter weight and composition for each treatment group in three (total n = 1,088) feedlot experiments. Steers were implanted with 0, 24, 36, 48, 60, 72, 84, or 96 mg of zeranol at approximately 140 d before slaughter. Cattle at each location were fed for the same number of days and slaughtered as a group. Zeranol dose had no effect on the chemical composition of bone, liver, or rib soft tissue with the following exceptions: zeranol decreased (P < .01) bone Ca concentration and increased (P < .07) liver P concentration. Zeranol implantation decreased medullary cavity anterioposterior (AP) diameters and AP cortical width (P < .08). Loads withstood by the bones up to flexure (P < .08) and the strain at flexure (P < .09) were inversely related to the quadratic of zeranol dose. However, modulus of elasticity at flexure and breaking increased numerically with zeranol dose. Stress withstood by bones at flexure was greater (P < .09) for implanted steers. Strain data indicate that metacarpals from steers receiving zeranol would exhibit less deformation upon loading to flexure (P < .09) than controls. These data indicate that administration of intermediate doses of zeranol altered bone deposition of Ca, which resulted in modified third metacarpal physical and mechanical characteristics.