Avaliação da eficácia de bupivacaína embebida em Gelfoam® no local do enxerto ósseo de crista ilíaca / Evaluation of the efficacy of bupivacaine soaked in Gelfoam® at the iliac crest bone graft site / Evaluación de la eficacia de la bupivacaina empapada en Gelfoam® en la región del injerto óseo de la cresta ilíaca

JUSTIFICATIVA E OBJETIVOS: Um número considerável de pacientes relata dor após coleta de enxerto da crista ilíaca anterior. Este estudo avaliou a eficácia da aplicação de bupivacaína embebida em uma esponja de gelatina absorvível (Gelfoam®) no local doador de osso e do uso parenteral de opioides no controle da dor pós-operatória. MÉTODO: Estudo prospectivo, duplo-cego, randomizado e controlado por placebo comparando a infiltração no período intraoperatório de 20 mL de bupivacaína (tratamento, grupo B) versus soro fisiológico (placebo) com Gelfoam embebida no local de coleta óssea da crista ilíaca em pacientes submetidos à cirurgia eletiva de coluna cervical. No período pós-operatório, a administração de cloridrato de hidromorfona (na sala de recuperação pós-anestésica e analgesia controlada pelo paciente) foi padronizada. Um escore de dor com base em escala visual analógica (EVA) com pontuação de zero a 10 foi usado para avaliar a intensidade da dor associada ao local doador. Os escores de dor e uso/frequência de narcóticos foram registrados 24 e 48 horas após a operação. Os médicos, pacientes, a equipe de enfermagem e os estatísticos desconheciam o tratamento usado. RESULTADOS: Os grupos eram semelhantes em idade, gênero e comorbidades. Não houve diferença significativa entre os grupos nos escores da EVA. As doses de narcótico foram significativamente menores no grupo B nos tempos de 24 e 48 horas (p < 0,05). CONCLUSÃO: Este estudo demonstrou que bupivacaína embebida em esponja de gelatina absorvível no local de coleta do enxerto ósseo de crista ilíaca (EOCI) reduziu o uso parenteral de opioides no pós-operatório.

BACKGROUND AND OBJECTIVE: A substantial number of patients report pain after graft harvest from the anterior iliac crest. This study examined the efficacy of local application of bupivacaine soaked in a Gelfoam® at the bone donor site in controlling postoperative pain and parenteral opioid use. METHOD: We performed a prospective, double-blind, randomized, placebo-controlled study comparing intraoperative infiltration of 20 mililiters of bupivacaine (treatment, group B) versus saline (placebo), with Gelfoam® soaked into the iliac crest harvest site for patients undergoing elective cervical spinal surgery. Postoperative administration of dihydromorphinone hydrochloride (post anesthesia care unit and patient-controlled analgesia) was standardized. A pain score based on a 10-point visual analog scale (VAS). was used to assess the severity of pain associated with donor site. Pain scores and narcotic use/frequency were recorded at the twenty-four and forty-eighth hour after the operation. Physicians, patients, nursing staff, and statisticians were blinded to the treatment. RESULTS: The groups were similar in baseline age, gender, and comorbidities. There was no significant difference between groups in VAS scores. Narcotic dosage, were significantly less in the Group B at 24 and 48 hours (p < 0.05). CONCLUSION: This study has demonstrated that bupivacaine soaked in gelfoam at the iliac bone graft harvest site reduced postoperative parenteral opioid usage.

JUSTIFICATIVA Y OBJETIVOS: Un número considerable de pacientes relata sentir dolor después de la recolección del injerto de la cresta ilíaca anterior. Este estudio evaluó la eficacia de la aplicación de bupivacaina empapada en una esponja de gelatina absorbible (Gelfoam®) en la región donadora del hueso y el uso parenteral de opioides en el control del dolor postoperatorio. MÉTODO: Realizamos un estudio prospectivo, doble ciego, aleatorio y controlado por placebo, comparando la infiltración en el período intraoperatorio de 20 mL de bupivacaina (tratamiento, grupo B) versus suero fisiológico (placebo) con Gelfoam empapado dentro de la región de la recolección ósea de la cresta ilíaca, en pacientes sometidos a la cirugía electiva de la columna cervical. En el período postoperatorio, la administración de clorhidrato de hidromorfona (unidad de recuperación y analgesia controlada por el paciente) se estandarizó. Un puntaje de dolor con base en la escala visual analógica (EVA) y un puntaje de 0 a 10 fueron usados para evaluar la intensidad del dolor asociada con la región donadora. Los puntajes de dolor y el uso/frecuencia de narcóticos se registraron 24 y 48 horas después de la operación. Los médicos, pacientes, el equipo de enfermería y los estadísticos no conocían el tratamiento usado. RESULTADOS: Los grupos eran similares en edad, sexo y comorbilidades. No hubo diferencia significativa entre los grupos en los puntajes de la EVA. Las dosis de narcótico fueron significativamente menores en el grupo B en los tiempos de 24 y 48 horas (p < 0,05). CONCLUSIONES: Este estudio demostró que la bupivacaina empapada en esponja de gelatina absorbible en la región de recolección del injerto óseo de la cresta ilíaca (EOCI) redujo el uso parenteral de opioides en el postoperatorio.

Evaluation of the efficacy of bupivacaine soaked in Gelfoam(®) at the iliac crest bone graft site.

BACKGROUND AND OBJECTIVE: A substantial number of patients report pain after graft harvest from the anterior iliac crest. This study examined the efficacy of local application of bupivacaine soaked in a Gelfoam(®) at the bone donor site in controlling postoperative pain and parenteral opioid use. METHOD: We performed a prospective, double-blind, randomized, placebo-controlled study comparing intraoperative infiltration of 20 mililiters of bupivacaine (treatment, group B) versus saline (placebo), with Gelfoam(®) soaked into the iliac crest harvest site for patients undergoing elective cervical spinal surgery. Postoperative administration of dihydromorphinone hydrochloride (post anesthesia care unit and patient-controlled analgesia) was standardized. A pain score based on a 10-point visual analog scale (VAS). was used to assess the severity of pain associated with donor site. Pain scores and narcotic use/frequency were recorded at the twenty-four and forty-eighth hour after the operation. Physicians, patients, nursing staff, and statisticians were blinded to the treatment. RESULTS: The groups were similar in baseline age, gender, and comorbidities. There was no significant difference between groups in VAS scores. Narcotic dosage, were significantly less in the Group B at 24 and 48 hours (p<0.05). CONCLUSION: This study has demonstrated that bupivacaine soaked in gelfoam at the iliac bone graft harvest site reduced postoperative parenteral opioid usage.

Changes in 3-dimensional bone structure indices in hypoparathyroid patients treated with PTH(1-84): a randomized controlled study.

Hypoparathyroidism (hypoPT) is characterized by a state of low bone turnover and high bone mineral density (BMD) despite conventional treatment with calcium supplements and active vitamin D analogues. To assess effects of PTH substitution therapy on 3-dimensional bone structure, we randomized 62 patients with hypoPT into 24 weeks of treatment with either PTH(1-84) 100 µg/day subcutaneously or similar placebo as an add-on therapy. Micro-computed tomography was performed on 44 iliac crest bone biopsies (23 on PTH treatment) obtained after 24 weeks of treatment. Compared with placebo, PTH caused a 27% lower trabecular thickness (p < 0.01) and 4% lower trabecular bone tissue density (p < 0.01), whereas connectivity density was 34% higher (p < 0.05). Trabecular tunneling was evident in 11 (48%) of the biopsies from the PTH group. Patients with tunneling had significantly higher levels of biochemical markers of bone resorption and formation. At cortical bone, number of Haversian canals per area was 139% higher (p = 0.01) in the PTH group, causing a tendency toward an increased cortical porosity (p = 0.09). At different subregions of the hip, areal BMD (aBMD) and volumetric BMD (vBMD), as assessed by dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT), decreased significantly by 1% to 4% in the PTH group. However, at the lumbar spine, aBMD decreased by 1.8% (p < 0.05), whereas vBMD increased by 12.8% (p = 0.02) in the PTH compared with the placebo group.

Antidiarrheal activity of Laurus nobilis L. leaf extract in rats.

In Jordan, the leaves of Laurus nobilis (Family Lauraceae) have been used in folk medicine for the treatment of diarrhea, among other ailments. However, the ethnopharmacology of this plant needs to be scientifically validated. The present work was carried out to evaluate the scientific basis of the antidiarrheal effect of the aqueous extract of L. nobilis leaf. L. nobilis leaf extract significantly inhibited castor oil-induced diarrhea (effective concentration producing 50% of the maximum response [EC(50)]=150±6.4 mg/kg) and reduced castor oil-induced enteropooling in rats (EC(50)=162±5.9 mg/kg). The extract also significantly inhibited intestinal transit of a charcoal meal and exerted a significant dose-dependent relaxation (EC(50)=71±5.3 mg/mL) on rat ileal smooth muscle. The aqueous extract tested positive for flavonoids, alkaloids, and tannins. These results established the efficacy of L. nobilis leaf aqueous extract as an antidiarrheal agent and are consistent with the popular use of the plant in the treatment of gastrointestinal disorders, particularly diarrhea.

The effect of dietary phosphorus and calcium level, phytase supplementation, and ileal infusion of pectin on the chemical composition and carbohydrase activity of fecal bacteria and the level of microbial metabolites in the gastrointestinal tract of pigs.

Two experiments with growing pigs were conducted to determine the effects of dietary P and Ca level, phytase supplementation, and ileal pectin infusion on ileal and fecal P and Ca balance, chemical composition of fecal mixed bacterial mass (MBM), and bacterial metabolic activity. Pigs (initial BW = 30 kg) were fitted with simple T-cannulas at the distal ileum. They were fed a low-P corn-soybean meal control diet (3 g of P/kg) or the control diet supplemented with monocalcium phosphate (MCP; 7 g of P/kg; Exp. 1) or 1,000 FTU phytase/kg (Exp. 2). The daily infusion treatments consisted of 60 g of pectin dissolved in 1.8 L of demineralized water or 1.8 L of demineralized water as the control infusion, infused via the ileal cannula. In each experiment, 8 barrows were assigned to 4 dietary treatments according to a double, incomplete 4 x 2 Latin square. The dietary treatments in Exp. 1 were the control (Con-) diet with water infusion; the control (Con+) diet with pectin infusion; the MCP diet with water infusion; and the MCP diet with pectin infusion. In Exp. 2, the pigs received the same Con- and Con+ treatments as in Exp. 1 and, in addition, the phytase-supplemented diet in combination with water or pectin infusion. After a 15-d adaptation period, feces were collected for 5 d followed by ileal digesta collection for 24 h. In Exp. 1, supplemental MCP increased (P

Effects of sevelamer hydrochloride and calcium carbonate on renal osteodystrophy in hemodialysis patients.

Disturbances in mineral metabolism play a central role in the development of renal bone disease. In a 54-wk, randomized, open-label study, 119 hemodialysis patients were enrolled to compare the effects of sevelamer hydrochloride and calcium carbonate on bone. Biopsy-proven adynamic bone disease was the most frequent bone abnormality at baseline (59%). Serum phosphorus, calcium, and intact parathyroid hormone were well controlled in both groups, although calcium was consistently lower and intact parathyroid hormone higher among patients who were randomly assigned to sevelamer. Compared with baseline values, there were no changes in mineralization lag time or measures of bone turnover (e.g., activation frequency) after 1 yr in either group. Osteoid thickness significantly increased in both groups, but there was no significant difference between them. Bone formation rate per bone surface, however, significantly increased from baseline only in the sevelamer group (P = 0.019). In addition, of those with abnormal microarchitecture at baseline (i.e., trabecular separation), seven of 10 in the sevelamer group normalized after 1 yr compared with zero of three in the calcium group. In summary, sevelamer resulted in no statistically significant changes in bone turnover or mineralization compared with calcium carbonate, but bone formation increased and trabecular architecture improved with sevelamer. Further studies are required to assess whether these changes affect clinical outcomes, such as rates of fracture.

Evidence that treatment with risedronate in women with postmenopausal osteoporosis affects bone mineralization and bone volume.

Risedronate is used in osteoporosis treatment. Postmenopausal women enrolled in the Vertebral Efficacy with Risedronate Therapy trial received either risedronate (5 mg/day) or placebo for 3 years. Subjects received calcium and vitamin D supplementation if deficient at baseline. Lumbar spine bone mineral density (BMD) was measured at baseline and at 3 years. Quantitative back-scattered electron imaging (qBEI) was performed on paired iliac crest biopsies (risedronate, n = 18; placebo, n = 13) before and after treatment, and the mineral volume fraction in the trabecular bone was calculated. Combining dual-energy X-ray absorptiometric values with the mineral volume fraction for the same patients allowed us to calculate the relative change in trabecular bone volume with treatment. This showed that the effect on BMD was likely to be due partly to changes in matrix mineralization and partly due to changes in bone volume. After treatment, trabecular bone volume in the lumbar spine tended to increase in the risedronate group (+2.4%, nonsignificant) but there was a significant decrease (-3.7%, P < 0.05) in the placebo group. Calcium supplementation with adequate levels of vitamin D led to an approximately 3.3% increase in mineral content in the bone material independently of risedronate treatment. This increase was larger in patients with lower matrix mineralization at baseline and likely resulted from correction of calcium/vitamin D deficiency as well as from reduced bone remodeling. Combining BMD and bone mineralization density distribution data show that in postmenopausal osteoporosis 3-year treatment with risedronate preserves or may increase trabecular bone volume, unlike placebo. This analysis also allows, for the first time, separation of the contributions of bone volume and matrix mineralization to the increase in BMD.

Three-year oral clodronate treatment does not impair mineralization of newly formed bone--a histomorphometric study.

Bisphosphonates have been used successfully in the treatment of malignant hypercalcemia and skeletal metastases. Recently, clodronate has been studied in adjuvant settings in primary breast cancer. However, long-term effect of adjuvant clodronate on bone histology has not been reported, whereas bone mineral density studies have been published. The aim of this study was to examine the effect and safety of long-term clodronate treatment on bone quality as measured by histomorphometric techniques from bone biopsies. A total of 299 patients with early stage breast cancer were randomized to receive adjuvant oral clodronate (1.6 g/day) or to a control group for 3 years. All patients had adjuvant treatment: premenopausal women had six cycles of chemotherapy and postmenopausal women had antiestrogen for 3 years. Trabecular bone quality was examined in transiliac bone biopsy specimens by using histomorphometric techniques in 28 clodronate treated and 35 control patients who were disease-free at 3 years and who allowed the biopsy specimen to be obtained. No statistically significant differences were found in the values of osteoid, mineral apposition rate, or mineralization lag time in bone biopsies between the clodronate and the control groups. Postmenopausal women who received two antiresorptive drugs, antiestrogen and clodronate, developed features of secondary hyperparathyroidism with increased eroded surface and osteoclast number. In premenopausal, women clodronate with adjuvant chemotherapy, which induced early menopause and rapid bone loss in most of the patients, seemed to conduct slight depression in bone formation. Three-year oral clodronate treatment does not impair mineralization of newly formed bone: however, clodronate with different adjuvant breast cancer treatments has a diverse impact on bone histomorphometry depending on the type of therapy.

Influence of estrogen therapy at conventional and high doses on the degree of mineralization of iliac bone tissue: a quantitative microradiographic analysis in postmenopausal women.

The beneficial skeletal effects of menopausal estrogen replacement therapy (HRT) are well documented. The role of secondary mineralization of bone as a determinant of bone quality is now well established in postmenopausal women treated with bisphosphonates or SERMs. The aim of present study was to investigate the effect of conventional and high doses of estrogen on the main parameters reflecting the degree of mineralization of bone (DMB). Bone biopsies were obtained from 20 women with osteopenia or osteoporosis before and after 24 months (18 to 38 months) of conventional HRT, and from 19 women who had received high doses of estradiol (implant 100 mg every 3-6 months for 1.5-20 years). DMB parameters (mean DMB, DMB Freq. Max. and Heterogeneity Index of the individual distributions of DMB) were measured using quantitative microradiography in cortical, cancellous, and total bone and expressed as g mineral/cm(3) bone. Values obtained in women before HRT were lower than those reported in pre- and postmenopausal control women. After conventional HRT, there was an increase in mean DMB (total bone) of 4.4 +/- 1.9% (mean +/- SEM) versus pre-treatment values (4.1 +/- 2.1% in cortical bone, 4.5 +/- 2.3% in cancellous bone); these differences did not reach statistical significance (P = 0.055). Results were similar for DMB Freq. Max. but Heterogeneity Index was not significantly changed. After high dose estradiol therapy, mean DMB (total bone) was 6.9 +/- 1.9% higher than in untreated women (8.6 +/- 2.1% in cortical bone, 6.5 +/- 2.1% in cancellous bone); this difference was statistically significant (P

Effects of raloxifene on bone density, biomarkers, and histomorphometric and biomechanical measures in ovariectomized cynomolgus monkeys.

OBJECTIVE: The purpose of this study was to determine the effect of raloxifene on bone density, strength, metabolism, and histomorphometric characteristics in ovariectomized cynomolgus monkeys. DESIGN: A prospective, longitudinal study was designed to examine the effects of conjugated equine estrogens (0.04 mg/kg, CEE) and raloxifene (1 or 5 mg/kg, R1 and R5, respectively) on bone density, biomarkers, histomorphometry, and strength. Control groups included ovariectomized and sham-operated monkeys. Treatment was initiated the day after ovariectomy and continued for 24 months. Bone biomarker data were collected at baseline and every 3 months after surgery. Bone mass was determined at baseline and every 6 months after ovariectomy. Iliac biopsies were collected at baseline and 16 months postovariectomy, and the second lumbar vertebra and left midshaft femur collected at necropsy were examined histomorphometrically. Bone biomechanical properties were determined for the right femur and vertebrae. RESULTS: Compared with the placebo-treated ovariectomized monkeys, the high-dose raloxifene group had lower levels of alkaline phosphatase, tartrate-resistant acid phosphatase, urinary CrossLaps (collagen degradation products), and greater bone mass in the lumbar vertebrae. In the endocortical compartment, the high-dose raloxifene group had significantly lower mineralizing surface, mineral apposition rate, and bone formation rate in the iliac biopsy collected at 16 months and lower bone formation rate in the second lumbar vertebra. Within the midshaft femur, low-dose raloxifene significantly decreased the osteonal and total bone formation rates and also prevented the decrease in Young's modulus induced by ovariectomy in the midshaft femur. CONCLUSIONS: High-dose raloxifene prevented the development of osteopenia in the ovariectomized monkey by reducing bone turnover, albeit to a lesser extent than CEE. Histomorphometric and biomarker data suggest that mechanisms underlying the effect of raloxifene differ somewhat from that of CEE.

Effects of daily treatment with parathyroid hormone on bone microarchitecture and turnover in patients with osteoporosis: a paired biopsy study.

We examined paired iliac crest bone biopsy specimens from patients with osteoporosis before and after treatment with daily injections of 400 U of recombinant, human parathyroid hormone 1-34 [PTH(1-34)]. Two groups of patients were studied. The first group was comprised of 8 men with an average age 49 years. They were treated with PTH for 18 months. The second group was comprised of 8 postmenopausal women with an average age 54 years. They were treated with PTH for 36 months. The women had been and were maintained on hormone replacement therapy for the duration of PTH treatment. Patients were supplemented to obtain an average daily intake of 1500 mg of elemental calcium and 100 IU of vitamin D. The biopsy specimens were subjected to routine histomorphometric analysis and microcomputed tomography (CT). Cancellous bone area was maintained in both groups. Cortical width was maintained in men and significantly increased in women. There was no increase in cortical porosity. There was a significant increase in the width of bone packets on the inner aspect of the cortex in both men and women. This was accompanied by a significant decrease in eroded perimeter on this surface in both groups. Micro-CT confirmed the foregoing changes and, in addition, revealed an increase in connectivity density, a three dimensional (3D) measure of trabecular connectivity in the majority of patients. These findings indicate that daily PTH treatment exerts anabolic action on cortical bone in patients with osteoporosis and also can improve cancellous bone microarchitecture. The results provide a structural basis for the recent demonstration that PTH treatment reduces the incidence of osteoporosis-related fractures.

Strontium distribution and interactions with bone mineral in monkey iliac bone after strontium salt (S 12911) administration.

The analysis of the interaction of strontium (Sr) with bone mineral is of interest because a new agent containing Sr (S 12911) has shown positive effects on bone mass in various animal models of osteoporosis and is currently being developed for preventive and curative treatment of postmenopausal osteoporosis. Iliac bone samples were obtained from 20 male monkeys: 4 untreated control animals, 12 animals sacrificed at the end of a 13-week treatment with high dose levels of S 12911 (750, 275, or 100 mg/kg/day orally), and 4 animals sacrificed 6 weeks after the end of a 13-week treatment with S 12911 (750 or 100 mg/kg/day orally). The distribution of Sr was determined and quantified by X-ray microanalysis. Changes at the crystal level were evaluated by X-ray diffraction and Raman microspectrometry. In the control animals, traces of Sr were found to be homogeneously distributed throughout the bone tissue. In the treated monkeys, Sr could only be detected in calcified matrix. In monkeys sacrificed at the end of the treatment, Sr was found to be dose-dependently incorporated into the mineral substance of the compact and cancellous bone. Sr was heterogeneously distributed with three to four times more Sr in new than in old compact bone, and approximately two and a half times more Sr in new than in old cancellous bone. The bone Sr content dramatically decreased in the animals sacrificed 6 weeks after the end of the treatment. Diffraction showed no significant changes in the characteristics of the crystal lattice. Sr appeared to be easily exchangeable from bone mineral and was slightly linked to mature crystals through ionic substitutions. Even at the highest dose level tested, less than 1 calcium ion out of 10 was substituted by 1 Sr ion in each crystal. In conclusion, taken up by bone, Sr was heterogeneously distributed with a higher concentration in new than in old bone but induced no major modifications of the bone mineral (crystallinity, crystal structure) at the crystal level. As a result, a treatment with S 12911 Sr salt should not induce any alteration of bone mineral.

Effects of 24R,25-dihydroxyvitamin D3 in combination with 1 alpha-hydroxyvitamin D3 in predialysis renal insufficiency: biochemistry and histomorphometry of cancellous bone.

The effect of combined administration of 24R,25-dihydroxyvitamin D3 (24,25-(OH)2D3) and 1 alpha-hydroxyvitamin D3 (1 alpha-(OH)D3) was studied in 24 non-dialyzed patients with chronic renal insufficiency (CRI), matched pairwise as to age, sex, and creatinine clearance (Cr.cl). Low Ca intake had been supplemented beforehand. Then, 1 alpha-(OH)D3 (mean dose 0.55 micrograms daily) was given orally to all patients for 3 months (T0 to T3). Subsequently, patients were assigned randomly to 6 months further treatment either with 1 alpha-(OH)D3 alone (Group A) or with 1 alpha-(OH)D3 plus a high dosage of 24,25-(OH)2D3 (50 micrograms orally, twice weekly) (Group B). Histomorphometry was performed at T0, T3, and T9. In both groups iPTH was equally suppressed, into the lower normal range. Whereas in Group A, serum Ca rose steadily and Cr.cl declined, in Group B both parameters levelled off between T6 and T9. At T9, in Group A the elevated resorption and osteoid indices had normalized markedly, but osteoblasts (Ob.Pm) and mineralizing boundaries (M.Bd) were depressed considerably between T3 and T9. In contrast, in Group B, preservation of Ob.Pm and improved mineralizing activity were observed (M.Bd at T9 > T3 > T0). Resorption indices hardly changed. In the patients with high Ob.Pm at T0, cancellous bone area increased significantly. This was not observed in Group A. Thus, in Group B, osteoblast recruitment appeared maintained and M.Bd appeared normalized. Decline of remodeling toward an adynamic state with an increased risk of hypercalcemia appeared prevented.

Skeletal response to recombinant human growth hormone (rhGH) in children treated with long-term corticosteroids.

Corticosteroid therapy causes osteopenia and growth retardation in children; such changes are associated with diminished rates of bone formation and turnover. Since growth hormone activates bone remodeling, the biochemical and skeletal responses to rhGH were evaluated in four pediatric patients, aged 12.8 +/- 3 years, with long-term corticosteroid use (5 +/- 2 years). Recombinant human growth hormone (rhGH), 0.125 mg/kg, was given 3 times/week by subcutaneous injection for 12 months. Iliac crest bone biopsies were obtained after double tetracycline labeling before and at the end of rhGH therapy; serum levels of calcium, phosphorus, alkaline phosphatase, parathyroid hormone (intact), 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D3, osteocalcin (BGP), and insulin-like growth factor-1 (IGF-1) were measured every 3 months during the treatment period. The average dose of prednisone was 0.24 +/- 0.05 mg/kg/day initially, and this did not change during the study. Serum calcium, phosphorus, alkaline phosphatase, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D3, and BGP were unchanged during the rhGH therapy, but the serum IGF-1 level increased by 71%, p < 0.01. Eroded bone perimeter and cancellous bone area did not change significantly during rhGH therapy. Bone formation rates rose from 423 +/- 475 to 781 +/- 407 microns2/mm2/day, p < 0.05, and the length of double tetracycline-labeled bone perimeter increased by 85%, p < 0.05. The bone formation rate in the growth hormone group exceeded the values of an age-matched reference group (14.3 +/- 3 years), 780 +/- 407 microns2/mm2/day versus 411 +/- 479 microns2/mm2/day, p < 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of bone turnover and prevention of bone atrophy in ovariectomized beagle dogs by the administration of 24R,25(OH)2D3.

In order to determine whether the administration of 24R,25(OH)2D3 had any beneficial effect on the regulation of bone turnover and the prevention of bone atrophy, we examined beagles for 31 months after ovariectomy (OVX). Fourteen beagle dogs (8.54 +/- 1.22 kg body wt-b.w.) were divided into four groups. Group 1 (n = 3) was the sham, and Group 2 (n = 3) served as the OVX control. In Group 3 (n = 4) and Group 4 (n = 4), 24,25-dihydroxyvitamin D3(24R,25(OH)2D3) was given daily at dose levels of 2 and 10 mcg/kg B.W., respectively. In Group 4, the dose level was increased to 100 mcg/kg by 17 months. During the experiments, urinary hydroxyproline (U-HPr), serum chemistry, serum bone gla-protein (BGP), and vitamin D metabolite levels were monitored. At the end of the experiment, bone mineral content (BMC) in the 6th and 7th lumbar vertebrae and right femur was determined by single photon absorptiometry. The left iliac bone sample was obtained after tetracycline labeling, and undecalcified sections were observed. In Group 2, excretion of U-HPr increased after OVX and had reached a level of approximately twice the baseline values by 10 months; then it gradually came down to the original level. In Group 3, however, U-HPr excretion remained at the same level as the baseline value, as it did in Group 1. In Group 4, it was remarkably reduced down to 50-60% of the baseline values. Serum BGP level was markedly reduced in Group 4. Serum 24,25(OH)2D levels were markedly increased in Groups 3 and 4.(ABSTRACT TRUNCATED AT 250 WORDS)

Control of primary osteosarcoma with chemotherapy.

High-dose methotrexate with citrovorum factor "rescue" (MTX-CF) produced an apparent complete response of the primary tumor in three patients with osteosarcoma. The response was sustained with MTX-CF, intra-arterial cis-diamminedichloroplatinum II (CDP) and Adriamycin (doxorubicin) for 18 months. Treatment was then electively discontinued. Local recurrence occurred in two patients, 6 and 4 months later, respectively. MTX-CF was reinstated and a complete response was again achieved in one patient. This has been maintained for 15+ months with MTX-CF and intra-arterial CDP administered for 13 of the 15+ months. Reinduction with MTX-CF failed in the second relapsed patient but an apparent remission was again achieved with radiation and intra-arterial CDP. This has been maintained with intravenous CDP, cyclophosphamide and phenylalanine mustard for 14+ months. A complete response in the primary tumor was still present in the nonrelapsed patient, 42 months from diagnosis. All patients have remained free of pulmonary metastases, 40+ to 42+ months from diagnosis.

Effect of sex hormones on bone in primary osteoporosis.

The effect of sex hormones on bone tissue was studied in 12 osteoporotic patients. Surfaces of bone undergoing formation and resorption were determined by quantitative microradiography of iliac crest biopsy samples before and after treatment with estrogens in 11 postmenopausal women and with testosterone in one gonadally competent man. Before treatment, bone resorption was greater than normal in all but one patient and bone formation was normal. After treatment, bone resorption decreased to within the normal range in all patients, and bone formation did not change significantly. Biochemical studies showed significant decreases in serum calcium, phosphorus, and alkaline phosphatase levels and in urinary excretion of calcium and hydroxyproline. These changes are believed to be the consequence of the effect of the hormones on bone. The data indicate that the major effect of sex hormones in osteoporosis is an inhibition of bone resorption.