[Osteoporotic vertebral fractures of the thoracic and lumbar spine]. / Osteoporotische Wirbelkörperfrakturen der Brust- und Lendenwirbelsäule.

The frequency of osteoporotic vertebral fractures in the clinical routine is increasing due to the demographic change. They are the most frequent fractures associated with osteoporosis and affect an especially morbid and vulnerable group of patients. These fractures often occur after minor trauma or spontaneously. Pain is the predominant symptom, whereas mechanical stability is mostly sufficient, in comparison to vertebral fractures after high-energy trauma, and is not a predominant indication for surgery. These fractures can be described using the classification for fractures associated with osteoporosis and the corresponding treatment recommendations are guided by them. Besides the specific treatment of osteoporotic vertebral fractures, a holistic treatment of patients taking pre-existing comorbidities into consideration is decisive. A mobilization as quickly as possible and treatment of the underlying osteoporosis are important to prevent further fractures.

Advantage of ostarine over raloxifene and their combined treatments for muscle of estrogen-deficient rats.

PURPOSE: Selective androgen (ostarine, OST) and estrogen (raloxifene, RAL) receptor modulators with improved tissue selectivity have been developed as alternatives to hormone replacement therapy. We investigated the combined effects of OST and RAL on muscle tissue in an estrogen-deficient rat model of postmenopausal conditions. METHODS: Three-month-old Sprague Dawley rats were divided into groups: (1) untreated non-ovariectomized rats (Non-OVX), (2) untreated ovariectomized rats (OVX), (3) OVX rats treated with OST, (4) OVX rats treated with RAL, (5) OVX rats treated with OST and RAL. Both compounds were administered in the diet. The average dose received was 0.6 ± 0.1 mg for OST and 11.1 ± 1.2 mg for RAL per kg body weight/day. After thirteen weeks, rat activity, muscle weight, structure, gene expression, and serum markers were analyzed. RESULTS: OST increased muscle weight, capillary ratio, insulin-like growth factor 1 (Igf-1) expression, serum phosphorus, uterine weight. RAL decreased muscle weight, capillary ratio, food intake, serum calcium and increased Igf-1 and Myostatin expression, serum follicle stimulating hormone (FSH). OST + RAL increased muscle nucleus ratio, uterine weight, serum phosphorus, FSH and luteinizing hormone and decreased body and muscle weight, serum calcium. Neither treatment changed muscle fiber size. OVX increased body and muscle weight, decreased uterine weight, serum calcium and magnesium. CONCLUSION: OST had beneficial effects on muscle in OVX rats. Side effects of OST on the uterus and serum electrolytes should be considered before using it for therapeutic purposes. RAL and RAL + OST had less effect on muscle and showed endocrinological side effects on pituitary-gonadal axis.

[Interdisciplinary extremity board in the treatment of complex injuries]. / Interdisziplinäres Extremitäten-Board in der Behandlung von Komplexverletzungen.

BACKGROUND: Interdisciplinary case conferences are well-established in the field of oncology in order to provide the best possible treatment for patients with complex disease patterns which overlap several disciplines. METHODS: After studying the available literature the aims, indications, frequency, patient enrolment and documentation modalities, disciplines necessary to create the reconstruction plan and evaluation parameters of the board, were agreed in an interdisciplinary discussion among colleagues. The utilization of the extremity board and demographic features of the cases presented in the extremity board within the first 6 months were subsequently descriptively analyzed. RESULTS: The agreed primary aim of an extremity board is the timely and transparent preparation of a high-quality holistic reconstruction plan for optimized treatment of a challenging patient collective with complex injuries of the extremities. Decisive interfaces of an extremity board are the participation of interdisciplinary disciplines, established enrolment and documentation modalities and a longitudinal analysis of parameters of the acute medical treatment, the long-term function and quality of life of those affected. The patient collective so far mostly includes men under 40 years old with traumatic soft tissue defects and combined injuries. On average, reconstruction plans for 1-2 patients were approved in an interdisciplinary team per session. CONCLUSION: The extremity board serves as a platform for coordinated planning of treatment for patients with complex injuries. The limited personnel and time resources represent the greatest challenge for the successful implementation. The extremity board enables a high degree of interdisciplinary networking. The digital registration and documentation modality within the internal hospital documentation system is of utmost relevance. The preparation of the reconstruction plan is of decisive importance for the qualitative success of treatment and the restoration of function. The longitudinal analysis of appropriate parameters is imperative to measure the quality of treatment.

Evaluation of ostarine as a selective androgen receptor modulator in a rat model of postmenopausal osteoporosis.

Selective androgen receptor modulators (SARMs) have shown beneficial effects on muscle wasting, general physical function and bone properties in male mammals. However, data on the effects of SARMs in postmenopausal osteoporotic bone are scarce. We evaluated the effects of the SARM drug ostarine on postmenopausal osteoporotic bone in a rat osteoporosis model. Ovariectomy was performed on 46 of 56 3-month-old female Sprague-Dawley rats. Eight weeks after ovariectomy, ostarine was orally administered daily for 5 weeks in dosages of 0.04 (low, OVX + Ost. 0.04), 0.4 (intermediate, OVX + Ost. 0.4), and 4 mg/kg (high, OVX + Ost. 4) body weight. Another ovariectomized group received no ostarine. Lumbar vertebrae and femora were removed for biomechanical, gene expression, ashing, and computer tomography analyses. Low dose showed no effects. The effects of intermediate and high doses were comparable overall. Improvements were mainly seen in structural properties such as bone mineral density and bone volume density. However, the effects in femora were superior to effects in vertebrae. Ostarine treatment for 5 weeks did not improve significantly biomechanical properties. mRNA expression of the receptor activator of NF-κB ligand decreased after treatment, and uterine weight increased. Serum levels of phosphorus increased following ostarine treatment in intermediate and high-dose groups. Short-term treatment of osteoporotic bone with ostarine leads to improvement of several microstructural bone indices. While we did not observe changes in biomechanics, it is conceivable that longer treatment may also improve biomechanical properties. Further studies are needed to characterize longer time effects and side effects of ostarine in osteoporosis.

Effect of zileuton on osteoporotic bone and its healing, expression of bone, and brain genes in rats.

Estrogen deficiency and aging are associated with osteoporosis, impaired bone healing, and lower cognitive performance. Close functional and physical connections occur between bone and the central nervous system. An anti-inflammatory drug, zileuton (which is an inhibitor of arachidonate 5-lipoxygenase), is known to have a positive effect on bone tissue repair and brain ischemia. We studied the effect of zileuton on osteopenic bone and its healing and on the genes considered to be crucial for the cross talks between bone and brain. Three-month-old Sprague-Dawley rats were ovariectomized or left untreated. After 8 wk, bilateral metaphyseal tibia osteotomy with plate osteosynthesis was performed in all rats. Ovariectomized rats were fed with food containing zileuton (1, 10, or 100 mg/kg body wt) for 5 wk. In tibiae, bone volume, callus and cortical volume, and gene expression of osteocalcin and alkaline phosphatase were enhanced by zileuton (10 or 100 mg); biomechanical properties and bone density were not changed. In femur, zileuton enlarged cortical volume distal and trabecular volume proximal, decreasing their density. The expression level of brain Sema3a, known to regulate bone mass positively, was downregulated after ovariectomy. In contrast, bone Sema4d, a negative regulator of bone mass, was upregulated in the tibia callus after ovariectomy, whereas zileuton treatment (10 or 100 mg) resulted in reverse effects. Here, we describe for the first time the expression of Rbbp4 mRNA and its increase in tibia after ovariectomy. Zileuton caused downregulation of Rbbp4 in the hippocampus and had an effect on bone healing, changed the expression of genes involved in cross talk between bones and brain, and may be a potent drug for further examination in estrogen deficiency-related dysfunction(s). NEW & NOTEWORTHY Zileuton, a 5-lipoxygenase inhibitor, increased bone volume, callus and cortical volume in osteotomized tibia, and trabecular and cortical volume in femur. Although the expression of Sema3a (positively regulating bone mass) in brain was downregulated and Sema4d (negatively regulating bone mass) was upregulated in tibia callus after ovariectomy, zileuton could counteract these effects. Rbbp4 (involved in age-related memory loss) was increased in tibia callus after ovariectomy.

Effect of the lipoxygenase-inhibitors baicalein and zileuton on the vertebra in ovariectomized rats.

Osteoporosis is one of the most common diseases worldwide. In osteoporosis, vertebral fractures represent a major burden. Lipoxygenase (LOX) inhibitors such as baicalein and zileuton may represent a promising therapeutic option owing to their antioxidative effects and suppression of various inflammatory processes in muscle and bone. The effect of these LOX inhibitors on the spine was studied in osteopenic rats. Female Sprague-Dawley rats were divided two times into five groups: four groups each were ovariectomized (OVX) and one control group was non-ovariectomized (NON-OVX). Eight weeks after ovariectomy, three concentrations of baicalein (1mg/kg body weight [BW], 10mg/kgBW, and 100mg/kgBW) were administered subcutaneously daily in three OVX groups for 4weeks. Similarly, zileuton was administered in three concentrations via food for 5weeks. In vivo computed tomography (pQCT) of the spine was performed before the treatments and at the end of the experiment. Lumbar vertebrae were subjected to a compression test, micro-CT, and ashing analyses. After baicalein treatment, cortical bone mineral density (BMD) was improved; trabecular connectivity and trabecular BMD were diminished at high dose. After zileuton treatment, the total BMD, anorganic weight, trabecular nodes, and trabecular area were improved. The in vivo stress-strain index was increased and alkaline phosphatase activity in serum was enhanced after both treatments. A dose-dependent effect was not clearly observed after both treatments. The treatments using baicalein for 4 and zileuton for 5weeks were not sufficient to change the biomechanical properties and bone volume fraction (BV/TV). Overall, baicalein improved the cortical bone parameters whereas zileuton had a favorable effect on the trabecular structure. Moreover, both treatments increased the bone formation rate. Longer trials, a combination of both LOX inhibitors, and their effect at the cellular and molecular levels should be investigated in further studies.

Comparison of parathyroid hormone and strontium ranelate in combination with whole-body vibration in a rat model of osteoporosis.

We investigated the combinatorial effects of whole-body vertical vibration (WBVV) with the primarily osteoanabolic parathyroid hormone (PTH) and the mainly antiresorptive strontium ranelate (SR) in a rat model of osteoporosis. Ovariectomies were performed on 76 three-month-old Sprague-Dawley rats (OVX, n = 76; NON-OVX, n = 12). After 8 weeks, the ovariectomized rats were divided into 6 groups. One group (OVX + PTH) received daily injections of PTH (40 µg/kg body weight/day) for 6 weeks. Another group (OVX + SR) was fed SR-supplemented chow (600 mg/kg body weight/day). Three groups (OVX + VIB, OVX + PTH + VIB, and OVX + SR + VIB) were treated with WBVV twice a day at 70 Hz for 15 min. Two groups (OVX + PTH + VIB, OVX + SR + VIB) were treated additionally with PTH and SR, respectively. The rats were killed at 14 weeks post-ovariectomy. The lumbar vertebrae and femora were removed for biomechanical and morphological assessment. PTH produced statistically significant improvements in biomechanical and structural properties, including bone mineral density (BMD) and trabecular bone quality. In contrast, SR treatment exerted mild effects, with significant effects in cortical thickness only. SR produced no significant improvement in biomechanical properties. WBVV as a single or an adjunctive therapy produced no significant improvements. In conclusion, vibration therapy administered as a single or dual treatment had no significant impact on bones affected by osteoporosis. PTH considerably improved bone quality in osteoporosis cases and is superior to treatment with SR.

Improvement of trochanteric bone quality in an osteoporosis model after short-term treatment with parathyroid hormone: a new mechanical test for trochanteric region of rat femur.

UNLABELLED: We have examined the changes induced in the trochanteric region of femur of ovariectomized rat after administration of estradiol and parathyroid hormone. We have developed a reproducible biomechanical test and produced trochanteric fractures to evaluate stiffness and strength of this region in addition to histomorphometry. INTRODUCTION: We investigated the short-term effects of parathyroid hormone (PTH) and estrogen (E) on the strength of the rat trochanteric region in a new mechanical test. METHODS: Forty-four 3-month-old female Sprague-Dawley rats were ovariectomized and 8 weeks later treated with soy-free diet (C), daily applications of orally supplied E (0.5 mg/kg food) or subcutaneously injected PTH (0.014 mg/kg), for 5 weeks, and an additional untreated group was added as sham-operated. The femurs were examined for biomechanical and histomorphometric changes. RESULTS: Our new mechanical test was validated in a right-left comparison. The PTH treatment induced significantly superior biomechanical results (F (max) = 225.3 N, stiffness = 314.9 N/mm) compared to E (F (max) = 182.9 N, stiffness = 237.2 N/mm), C (F (max) = 166.03 N, stiffness = 235.56 N/mm), and sham (F (max) = 192.1 N, stiffness = 267.2 N/mm). Animals of the PTH group demonstrated a significantly improved trabecular bone structure and area (75.67%) in comparison to the E (61.04%) and C (57.18%) groups. CONCLUSION: Our new biomechanical test is valid and produces trochanteric fracture. Our results show that the short-term antiosteoporotic effects of PTH are in the trochanteric region of ovariectomized rat superior to E.

Effects of isoflavones equol and genistein on bone quality in a rat osteopenia model.

Phytoestrogens might be an alternative medication in prophylaxis and treatment of osteoporosis. In this study, the osteoprotective effects of genistein (GEN) and equol (EQO) were evaluated. After ovariectomy, 44 rats received soy-free food (Control, C) and developed substantial osteoporosis over the course of two months. After that period, the rats were divided into different groups and fed estradiol (E), GEN or EQO for 35 days. To analyze the osteoprotective effects of the tested substances, bone biomechanical properties and histomorphometric changes of the lumbar vertebrae were evaluated. In analyzing the vertebral body compression strength, we found that the EQO (103.8%) and GEN (96.8%) groups reached similar levels relative to the E group, while the C group reached 77.7% of the biomechanical properties of the E group. EQO was significantly superior to C. The histomorphometric evaluation demonstrated an increased number of nodes in EQO- and E-treated rats compared to GEN- and C-treated rats. E led to an improvement of cortical as well as trabecular bone, an advantage that was only partly seen in the other groups. Treatment with phytoestrogens induced improved bone quality. EQO and GEN might be alternatives for hormone replacement therapy, although further studies are needed to elucidate possible side effects.

Evaluation of bone quality and quantity in osteoporotic mice--the effects of genistein and equol.

The technology of gene manipulation is often used in mice. A crucial point for osteoporosis research is the evaluation of biomechanical and morphologic parameters. These parameters, however, are difficult to measure in mice. Nevertheless, this study demonstrates the capability of using techniques for the evaluation of bone quality and quantity after various treatments in osteopenic mice. After ovariectomy, 60 C57BL/6J mice were divided into 4 groups and were fed a soy-free diet (C) supplemented with estradiol, genistein or equol for 3 months. To analyze the osteoprotective effects of the tested supplements, we evaluated the bone biomechanical properties, histomorphometric changes and bone mineral density of the proximal tibiae metaphysis. The biomechanical parameters of genistein (GEN) were shown to be similar to those levels observed with estradiol (E). The biomechanical parameters of both GEN and E were significantly superior to those observed with C. Supplementation with equol (EQO) demonstrated higher mean biomechanical values than those observed with C. The histomorphometric evaluation demonstrated an increased number of nodes in mice treated with GEN and E as compared to the mice treated with EQO and C. Treatment with E and EQO led to improved cortical bone, which was only partly seen with the mice treated with GEN. The analysis of the bone mineral density (BMD) demonstrated that treatment with GEN and E resulted in a significant improvement as compared to the mice treated with C, while the cancellous density was significantly increased in all of the supplementation groups. This study conclusively demonstrated that bone quality and quantity parameters can be measured in mice. Furthermore, biomechanical and morphologic evaluations were shown to be reliable for use in mice. Further studies may combine these techniques with gene manipulation technology to better understand osteoporosis. Treatment with GEN resulted in improved biomechanical results and enhancement of morphologic parameters.

Effect of testosterone, raloxifene and estrogen replacement on the microstructure and biomechanics of metaphyseal osteoporotic bones in orchiectomized male rats.

INTRODUCTION: Currently, osteoporosis research is rarely undertaken in males but an increase in male life expectancy in the company of hypogonadism suggests the necessity for potential therapeutic options. MATERIALS AND METHODS: In this study, the changes in bone structure under standardized testosterone- (T), raloxifene- (R) and estrogen (E)-supplemented diets were analyzed in osteoporotic castrated male rats. RESULTS: Unexpected biomechanical results could be only explained by the histomorphometry, but not by BMD measurements obtained from the qCT. All tested substances showed a significant improvement in the trabecular network (trabecular bone area for C: 2.55 mm(2), T: 4.25 mm(2), R: 4.22 mm(2) and E: 4.28 mm(2)), and suggests that the bone structure was preserved. For the metaphyseal cortical bone, a significant loss was detected in T (CBP: 18.7%) compared to R (CBP: 30.0%), E (CBP: 26.8%) and even to the osteoporotic control (CBP: 28.6%). This explains the observed early mechanical final failure after T supplementation. However, due to the preserved trabecular bone in T, the occurrence of the first microfractures (yL: 49 +/- 21.4 N) was significantly later than in the osteoporotic control (yL: 39.5 +/- 15.5 N). Raloxifene performed well in hindering the bone loss associated with osteoporosis. However, its effect (yL: 83.3 +/- 16.5 N) did not approach the protective effect of E (yL: 99.2 +/- 21.1 N). CONCLUSION: Testosterone only preserved the deterioration of the trabecular bone but not of the cortical bone. Raloxifene prevented the bone loss associated with osteoporosis at all bony structures. This effect did not approach the protective effect of estrogen on trabecular bone, but it is more suitable for male individuals because it has no feminizing effects on the subject.

Vitex agnus castus as prophylaxis for osteopenia after orchidectomy in rats compared with estradiol and testosterone supplementation.

Osteoporosis research undertaken in males is rare and there are only a few therapeutic options. Phytoestrogens might be a safe alternative for prophylaxis. Sixty 3-month-old male rats were orchidectomized and divided into five groups. The groups either received soy-free food (C), estradiol (E), testosterone (T) or Vitex agnus castus in different concentrations (AC high/AC low) for 12 weeks. The tibia metaphysis was tested biomechanically and histomorphometrically. The AC high group reached 87% of the biomechanical values of the estradiol group and was significantly superior to the control group. Testosterone supplementation resulted in poor biomechanical properties. The cortical bone parameters of the AC group were similar to the control group, while supplementation with estradiol and testosterone demonstrated a reduction of cortical bone. The AC high group reached 88.4% of trabecular bone area, 80.7% of trabecular number and 66.9% of the number of trabecular nodes compared with estradiol supplementation. Vitex agnus castus demonstrated osteoprotective effects in males. It preserves the cortical as well as the trabecular bone and might be a safe alternative for HRT. Testosterone supplementation has positive effects on trabecular bone, which are concurrently counteracted by the loss of cortical bone.