Treatment of simple bone cysts of the humerus by intramedullary nailing and steroid injection.

BACKGROUND: Simple bone cysts (SBCs) are common benign lytic bone lesions in children. This study focused on exploring a clinical treatment method, minimally invasive intramedullary decompression and drainage with elastic stable intramedullary nailing (ESIN) combined with intralesional injections of steroids, and evaluated its effectiveness, complications and morbidity through functional and radiographic outcomes. METHODS: The postoperative recovery of 18 children who suffered from SBCs of humerus was evaluated (mean follow-up, 40 months) from January 2009 to December 2016. These patients (11 males, 7 females; 8 in the left, 10 in the right; mean age, 10.9 years old) were treated with minimally invasive intramedullary decompression and drainage with ESIN combined with intralesional injections of steroids. The diagnosis was based on not only pre-operative typical medical images (X-rays/CT/MRI) but also surgical findings and pathological diagnosis. Radiological and functional outcomes were evaluated according to Capanna and Musculoskeletal Tumor Society (MSTS) score. The interclass differences were analyzed by t-test. RESULTS: According to Capanna and MSTS criteria, after treatment, 14 patients made full recoveries which was presented by all the cysts filled with bone tissue, and 4 patients made partially recoveries, which were presented by cystic spaces partially filled with low density bone. All the cysts responded to treatment method, and there was no cyst recurrence. All except 2 patients had good functional results. One of the two patients had irritation of the end of the nail and one patient had a valgus deformity. CONCLUSIONS: Treatment for SBCs of humerus by minimally invasive intramedullary decompression and drainage with ESIN combined with intralesional injections of steroids is safe, effective and convenient. The clinical effect is satisfactory and worth popularizing.

Cartilage Homeostasis Affects Femoral Head Necrosis Induced by Methylprednisolone in Broilers.

(1) Background: Since the large-scale poultry industry has been established, femoral head necrosis (FHN) has always been a major leg disease in fast-growing broilers worldwide. Previous research suggested that cartilage homeostasis could be taken into consideration in the cause of FHN, but the evidence is insufficient. (2) Methods: One-day-old broiler chickens were randomly divided into three groups, 16 broilers per group. The birds in group L were injected intramuscularly with methylprednisolone (MP) twice a week for four weeks (12.5 mg·kg-1). The birds in group H were injected intramuscularly with MP (20 mg·kg-1·d-1) for 7 d (impulse treatment). The birds in group C were treated with sterile saline as a control group. Broilers were sacrificed at 42 and 56 d. Blood samples were collected from the jugular vein for ELISA and biochemical analysis. Bone samples, including femur, tibia, and humerus, were collected for histopathological analysis, bone parameters detection, and real-time quantitative PCR detection. (3) Results: The FHN broilers in group L and H both showed lower body weight (BW) and reduced bone parameters. In addition, the MP treatment resulted in reduced extracellular matrix (ECM) anabolism and enhanced ECM catabolism. Meanwhile, the autophagy and apoptosis of chondrocytes were enhanced, which led to the destruction of cartilage homeostasis. Moreover, the impulse MP injection increased the portion of birds with severer FHN, whereas the MP injection over a long period caused a more evident change in serum cytokine concentrations and bone metabolism indicators. (4) Conclusions: The imbalance of cartilage homeostasis may play a critical role in the development of FHN in broilers. FHN broilers induced by MP showed a more pronounced production of catabolic factors and suppressed the anabolic factors, which might activate the genes of the WNT signal pathway and hypoxia-inducible factors (HIFs), and then upregulate the transcription expression of ECM to restore homeostasis.

Local application of a gentamicin-loaded thermo-responsive hydrogel allows for fracture healing upon clearance of a high Staphylococcus aureus load in a rabbit model.

Antibiotic-loaded biomaterials (ALBs) have emerged as a potential useful adjunctive antimicrobial measure for the prevention of infection in open fracture care. A biodegradable thermo-responsive poly(N-isopropylacrylamide) grafted hyaluronic acid (HApN) hydrogel loaded with gentamicin has recently been shown to prevent implant-related infection in a rabbit osteosynthesis model. The primary aim of this study was to determine the influence of this HApN hydrogel on bone healing at an early stage (4 weeks). A rabbit humeral osteotomy model with plating osteosynthesis was used to compare fracture healing in rabbits receiving the hydrogel as compared with control animals. The secondary aim was to observe fracture healing in groups treated with and without antibiotic-loaded hydrogel in the presence of bacterial contamination. In all groups, outcome measures were mechanical stability and histological score, with additional quantitative bacteriology in the inoculated groups. Application of the HApN hydrogel in non-inoculated rabbits did not significantly influence humeral stiffness or histological scores for fracture healing in comparison to controls. In the inoculated groups, animals receiving the bacterial inoculum without hydrogel were culture-positive at euthanasia and found to display lower humeral stiffness values and higher histopathological scores for bacterial presence in comparison with equivalents receiving the gentamicin-loaded HApN hydrogel, which were also infection-free. In summary, our data showed that HApN was an effective antibiotic carrier that did not affect fracture healing. This data supported its suitability for application in fracture care. Addition of osteopromotive compounds could provide further support for accelerating fracture healing in addition to successful infection prophylaxis.

On the influence of surface coating on tissue biomechanics - effects on rat bones under routine conditions with implications for image-based deformation detection.

BACKGROUND: Biomechanical testing using image-based deformation detection techniques such as digital image correlation (DIC) offer optical contactless methods for strain and displacement measurements of biological tissues. However, given the need of most samples to be speckled for image correlation using sprays, chemical alterations with impact on tissue mechanicals may result. The aim of this study was to assess the impact of such surface coating on the mechanical properties of rat bones, under routine laboratory conditions including multiple freeze-thaw cycles. METHODS: Two groups of rat bones, highly-uniform and mixed-effects, were assigned to six subgroups consisting of three types of surface coating (uncoated, commercially-available water- and solvent-based sprays) and two types of bone conditions (periosteum attached and removed). The mixed-effects group had undergone an additional freeze-thaw cycle at - 20 degrees. All bones underwent a three-point bending test ranging until material failure. RESULTS: Coating resulted in similar and non-significantly different mechanical properties of rat bones, indicated by elastic moduli, maximum force and bending stress. Scanning electron microscopy showed more pronounced mechanical alterations related to the additional freeze-thaw cycle, with fewer cracks being present in a bone from the highly-uniform group. CONCLUSIONS: This study has concluded that surface coating with water- or solvent-based sprays for enhancing image correlation for DIC and having an additional freeze-thaw cycle do not significantly alter mechanical properties of rat bones. Therefore, this method may be recommended as an effective way of obtaining a speckled pattern.

Bone-site-specific responses to zoledronic acid.

OBJECTIVES: Bisphosphonates are widely used to treat bone diseases such as osteoporosis. However, they may cause osteonecrosis of the jaw. Here, we investigated whether in vivo exposure to bisphosphonates has a different effect on long bone and jaw osteoclasts, and on the turnover of these different bones. MATERIALS AND METHODS: Zoledronic acid (0.5 mg kg-1 weekly) was administered intraperitoneally to 3-month-old female mice for up to 6 months. The effects on the number of osteoclasts, bone mineralization and bone formation were measured in the long bones and in the jaw. RESULTS: Long-term treatment with zoledronic acid reduced the number of jaw bone marrow cells, without affecting the number of long bone marrow cells. Zoledronic acid treatment did not affect the number of osteoclasts in vivo. Yet, the bisphosphonate increased bone volume and mineral density of both long bone and jaw. Interestingly, 6 months of treatment suppressed bone formation in the long bones without affecting the jaw. Unexpectedly, we showed that bisphosphonates can cause molar root resorption, mediated by active osteoclasts. CONCLUSIONS: Our findings provide more insight into bone-site-specific effects of bisphosphonates and into the aetiology of osteonecrosis of the jaw. We demonstrated that bisphosphonates can stimulate osteoclast activity at the molar roots.

The utility of bone scintigraphy in the assessment of mandibular metabolism during long-term bisphosphonate administration.

The duration of antiresorptive therapy is an important risk factor for medication-related osteonecrosis of the jaw. We performed a pilot study using quantitative analysis by bone scintigraphy to test the hypothesis that mandibular metabolism is affected by long-term bisphosphonate (BP) therapy. Our primary objectives were to assess changes in bone metabolism of the mandible in response to long-term BP therapy and compare the bone metabolism changes of the mandible with other bone sites. We compared the metabolic difference at the site in the mandible unaffected by disease, the humerus and the femur between 14 osteoporosis patients who were being treated with BP (BP group) and 14 patients who were not being treated with BP (control group) using a quantitative analysis and bone scintigraphy. Study endpoints were the mean and maximum bone uptake values (BUVs) quantified using bone scintigraphy images of the mandible, humerus and femur. Quantified images of the site in the mandible unaffected by disease had significantly higher mean and maximum BUVs compared to the controls (mean, 0.74 vs. 0.49, p = 0.019; max., 1.29 vs. 0.85, p = 0.009, respectively). The mean and maximum BUV of femur ROIs in the BP group were significantly lower than those in control patients (mean BUV, 0.23 vs. 0.30, p = 0.039; max. BUV, 0.43 vs. 0.53, p = 0.024, respectively). This is the first report of mandible changes in response to long-term BP treatment, using bone scintigraphy. The results using bone scintigraphy demonstrated that the bone metabolism of the intact mandible is affected by a long-term administration of BP.

In Utero Tenofovir Exposure Is not Associated With Fetal Long Bone Growth.

BACKGROUND: Despite widespread use of tenofovir disoproxil fumarate (TDF) in pregnant and breastfeeding women, few data exist on fetal bone development after in utero TDF exposure. We evaluated fetal long bone growth in human immunodeficiency virus (HIV)-infected pregnant woman/fetus dyads in Cape Town, South Africa. METHODS: Women were recruited from primary care antenatal services and underwent ultrasonography to determine femur (FLZ) and humerus (HLZ) length z scores. The duration of in utero TDF exposure was calculated in weeks. Linear regression models were applied to assess the associations between the duration of in utero TDF exposure and change in FLZ and HLZ. RESULTS: A total of 646 woman/fetus dyads contributed 1376 ultrasonographic scans to this analysis: 132 dyads with ≥25 weeks, 326 with 10-24 weeks, and 188 with <10 weeks of TDF exposure. Women receiving TDF for ≥25 weeks were older than those receiving TDF for 10-24 or <10 weeks (median age, 31 vs 28 and 28 years, respectively; P < .01), and had lower HIV RNA levels (median log10 HIV RNA level, 1.59 vs 4.08 and 3.83, respectively; P < .01). Throughout gestation, overall median FLZ and HLZ were 0.30 (interquartile range, -0.03 to 0.63) and 0.22 (-0.26 to 0.59) respectively. In multivariate analysis, there was no association between duration of in utero TDF exposure per 1-week increment and change in FLZ (ß = .00; P = .51) or change in HLZ (ß = .00; P = .40). Results were similar using mixed-effects models. CONCLUSIONS: Although longer follow-up is needed, these in utero data are reassuring and support the continued use of TDF in pregnancy.

Bone and bone marrow involvement in sarcoidosis.

Bone and bone marrow involvement in sarcoidosis have been infrequently reported. We aimed to describe the clinical features, radiological descriptions, pathological examinations, and outcomes of three patients with osseous sarcoidosis and one patient with bone marrow sarcoidosis seen at our institution. Our case series included fluorodeoxyglucose positron emission tomography descriptions in assessing the whole-body extent of sarcoidosis. In the era of advanced imaging, large bone and axial skeleton sarcoidosis lesions are more common than previously reported.

Changes of elastic constants and anisotropy patterns in trabecular bone during disuse-induced bone loss assessed by poroelastic ultrasound.

Currently, the approach most widely used to examine bone loss is the measurement of bone mineral density (BMD) using dual X-ray absorptiometry (DXA). However, bone loss due to immobilization creates changes in bone microarchitecture, which in turn are related to changes in bone mechanical function and competence to resist fracture.Unfortunately, the relationship between microarchitecture and mechanical function within the framework of immobilization and antiresorptive therapy has not being fully investigated. The goal of the present study was to investigate the structure­function relationship in trabecular bone in the real-world situations of a rapidly evolving osteoporosis(disuse), both with and without antiresorptive treatment. We evaluated the structure­function relationship in trabecular bone after bone loss (disuse-induced osteoporosis)and bisphosphonate treatment (antiresorptive therapy using risedronate) in canine trabecular bone using lCT and ultrasound wave propagation. Microstructure values determined from lCT images were used into the anisotropic poroelastic model of wave propagation in order to compute the apparent elastic constants (EC) and elastic anisotropy pattern of bone. Immobilization resulted in a significant reduction in trabecular thickness (Tb.Th) and bone volume fraction (BV/TV), while risedronate treatment combined with immobilization exhibited a lesser reduction in Tb.Th and BV/TV, suggesting that risedronate treatment decelerates bone loss, but it was unable to fully stop it. Risedronate treatment also increased the tissue mineral density (TMD), which when combined with the decrease in Tb.Th and BV/TV may explain the lack of significant differences invBMD in both immobilization and risedronate treated groups. Interestingly, changes inapparent EC were much stronger in the superior­inferior (SI) direction than in the medial­lateral (ML) and anterior­posterior (AP) anatomical directions, producing changes in elastic anisotropy patterns. When data were pooled together, vBMD was able to explain 58% of ultrasound measurements variability, a poroelastic wave propagation analytical model (i.e., BMD modulated by fabric directionality) was able to predict 81%of experimental wave velocity variability, and also explained 91% of apparent EC and changes in elastic anisotropy patterns. Overall, measurements of vBMD were unable to distinguish changes in apparent EC due to immobilization or risedronate treatment.However, anisotropic poroelastic ultrasound (PEUS) wave propagation was able to distinguish functional changes in apparent EC and elastic anisotropy patterns due to immobilization and antiresorptive therapy, providing an enhanced discrimination of anisotropic bone loss and the structure­function relationship in immobilized and risedronate-treated bone, beyond vBMD.

Evaluation of extremity tissue and bone injury after intraosseous hypertonic saline infusion in proximal tibia and proximal humerus in adult swine.

BACKGROUND: Hypertonic saline (HTS) has been reported as a treatment for sever traumatic brain injury and hemorrhagic shock and current clinical guidelines recommend it. Intraosseous (IO) infusion is often needed in the pre-hospital and combat settings to administer life-saving treatments. However, the safety of IO HTS infusion is not clear. The aim of our study was to evaluate the clinical and histological outcome of HTS IO infusion into the extremity of a large animal model. METHODS: We conducted a randomized comparative study of adult pigs that were infused intraosseously with one of the following solutions: 7.5% HTS, 3% HTS or normal 0.9% isotonic saline. The animals were observed daily for infection, necrosis and gait (5 point Tarlov score) up to 5 days. Five days after infusion, necropsy and histological analysis was performed using a validated scale of tissue necrosis. RESULTS: The mean Tarlov gait scores were similar in all arms and all animals showed a score of 4 (normal ambulation) by day 5. During the 5 day observation period, there were no signs of infection or tissue abnormalities. Histological examinations showed no indication of necrosis, or abnormal bone and muscle healing (p < 0.05). CONCLUSION: We observed regular tissue morphology and normal gait scores over the 5 day observation period. There was an absence of gross tissue necrosis and microscopic ischemia post IO HTS infusion in this swine model. This data confirms the clinical safety of IO HTS infusion and highlights its use as an alternative lifesaving treatment.

Steroid injections in the treatment of humeral unicameral bone cysts: long-term follow-up and review of the literature.

BACKGROUND: Retrospective evaluation of long-term effectiveness of the steroid injections treatment in patients with unicameral bone cysts (UBC). METHODS: From January 1993 to April 2005, 23 children affected by proximal humeral UBC were evaluated according to the Neer-Cole classification system and treated with serial methylprednisolone acetate's injections. The patients were followed up at 1, 3, 6 and 12 months and then every year until the adolescence. RESULTS: After treatment, in 15 out of 23 patients (65.2%), the humeral cysts were referred, respectively, as Grade 1 and in four as Grade 2. In 4 patients, a refracture occurred. Statistical analysis showed an overall good response in 82.6% of patients at the end of the follow-up. Minor complication including skin discoloration accounted for 13.04%. CONCLUSIONS: The steroid injections showed to be an alternative excellent treatment for UBC, with complete healing of the lesions in the majority of cases. This procedure is not expensive, mini-invasive, with low surgical risk and short hospitalization.

The effect of sterilization on the mechanical properties of intact rabbit humeri in three-point bending, four-point bending and torsion.

Load bearing bone allografts are used to replace the mechanical function of bone that has been removed or to augment bone that has been damaged in trauma. In order to minimize the risk of infection and immune response, the bone is delipidated and terminally sterilized prior to implantation. The optimal method for bone graft sterilization has been the topic of considerable research. Recently, supercritical carbon dioxide (SCCO(2)) treatments have been shown to terminally sterilize bone against a range of bacteria and viruses. This study aimed to evaluate the effect of SCCO(2) treatment compared with two doses of gamma irradiation, on the mechanical properties of whole bone. Paired rabbit humeri were dissected and randomly assigned into either SCCO(2) control, SCCO(2) additive or gamma irradiation at 10 or 25 kGy treatment groups. The bones were mechanically tested in three-point and four-point bending and torsion, with the lefts acting as controls for the treated rights. Maximum load, energy to failure and stiffness were evaluated. This study found that SCCO(2) treatment with or without additive did not alter maximum load, energy to failure or stiffness significantly under any loading modality. Gamma irradiation had a deleterious dose dependant effect, with statistically significant decreases in all mechanical tests at 25 kGy; while at 10 kGy there were reductions in all loading profiles, though only reaching statistical significance in torsion. This study highlights the expediency of SCCO(2) treatment for bone allograft processing as terminal sterilization can be achieved while maintaining the intrinsic mechanical properties of the graft.

Effects of an anti-platelet drug on the prevention of steroid-induced osteonecrosis in rabbits.

OBJECTIVE: To investigate the effects of an anti-platelet drug (clopidogrel) on the prevention of steroid-induced osteonecrosis (ON) in rabbits. METHODS: Adult male Japanese white rabbits were divided into two groups and treated as follows: one group received daily clopidogrel mixed in normal saline (AP; n = 35), the other received only normal saline (NS; n = 30). One week after the administration, all rabbits were injected once intramuscularly with 20 mg/kg of methylprednisolone acetate into the right gluteus medius muscle. Three weeks after, both the femora and humeri were examined histopathologically for the presence of ON. The platelet aggregation assay and hematological examinations were performed before and after the steroid injection. RESULTS: The incidence of ON in the AP group (48.5%) was significantly lower than that observed in the NS group (73.3%). The platelet aggregations in the AP group were significantly inhibited by the administration of clopidogrel. The levels of total cholesterol and triglycerides showed no significant differences between the AP and NS group. CONCLUSION: The present experimental study demonstrated that the administration of an anti-platelet drug prevented steroid-induced ON in rabbits and that platelet aggregation seems to be one of the possible factors involved in the pathogenesis of steroid-induced ON.

Widespread osteonecrosis in children with leukemia revealed by whole-body MRI.

BACKGROUND: Confirmation of early long-bone epiphyseal osteonecrosis in pediatric patients with leukemia allows for medical and surgical intervention before articular surface collapse. MRI detects early osteonecrosis, but multiple focused MR images are required to capture all lesions. QUESTIONS/PURPOSES: We determined whether whole-body MRI (WB-MRI) could (1) assist in diagnosing long-bone epiphyseal and other osteonecroses, (2) characterize articular surface involvement, and (3) detect preferential sites for osteonecrosis. PATIENTS AND METHODS: We retrospectively reviewed prospectively collected data on all 11 pediatric patients newly diagnosed with leukemia who had musculoskeletal pain develop that persisted 4 weeks or more during leukemia treatment. All were screened for osteonecrosis by WB-MRI, which consisted of a one-time scan of the entire body. Osteonecrosis was defined as circumscribed lesions with a distinct rim of low signal intensity in the normally high-intensity marrow on T1-weighted images and high signal intensity in the normally low-intensity marrow on short-tau inversion recovery images. RESULTS: WB-MRI confirmed osteonecrosis in nine of 11 patients. All patients had multisite lesions; eight had long-bone epiphyseal lesions, which comprised 66 of 129 (51%) of all lesions. Osteonecrosis involving greater than 50% of the epiphyseal surface was present in 57% of distal femoral and proximal tibial lesions. All humeral and femoral head lesions involved more than 1/3 of the medial surface volume but were asymptomatic. No articular collapse was present. All osteonecrotic lesions were more common in the lower extremities. CONCLUSIONS: WB-MRI confirmed early epiphyseal osteonecrosis, with quantification of articular surface involvement. Lower limbs were preferentially affected, but asymptomatic humeral head osteonecrosis was present in five of nine patients. LEVEL OF EVIDENCE: Level IV, diagnostic study. See Instructions for Authors for a complete description of levels of evidence.

Strontium doping of bone graft extender.

BACKGROUND AND PURPOSE: Allografts are often used during revision hip replacement surgery for stabilization of the implant. Resorption of the allograft may exceed new bone formation, and instability of the prosthesis can develop. We investigated whether strontium could regulate the imbalance of fast resorption of allograft and slower formation of new bone, because it is both an anabolic and an anticatabolic agent. METHOD: Strontium was added to the implant interface environment by doping a hydroxyapatite bone graft extender. 10 dogs each received 2 experimental titanium implants. The implants were inserted within a 2.7-mm concentric gap in cancellous bone. The gap was filled with 50% (v/v) allograft mixed with 50% bone graft extender. The extender either had 5% strontium doping (SrHA) or was undoped (HA). After 4 weeks, osseointegration and mechanical fixation were evaluated by histomorphometry and by push-out test. RESULTS: SrHA bone graft extender induced a 1.2-fold increase in volume of new bone, a 1.2-fold increase in allograft remaining in the gap, and a 1.4-fold increase in surface area of the bone graft extender material in contact with new bone compared to HA bone graft extender. All these increases were statistically significant. SrHA bone graft extender did not significantly improve ongrowth of bone onto the implants or improve any of the mechanical push-out parameters compared to HA bone graft extender. INTERPRETATION: Doping of the HA bone graft extender with 5% strontium increased gap healing, preserved more of the allograft in the gap, and increased the ongrowth of bone onto the bone graft extender material, but did not improve mechanical fixation.

Chronic Nicotine Exposure Minimally Affects Rat Supraspinatus Tendon Properties and Bone Microstructure.

Cigarette smoking is the largest cause of preventable deaths, and a known risk factor for musculoskeletal issues including rotator cuff tendon tears. Tendon degeneration is believed to be due in part to changes in tendon cell health and collagen structure. Several studies have demonstrated that exposure to nicotine negatively impacts tendon healing, but surprisingly, nicotine exposure was shown to increase rat supraspinatus tendon stiffness. In order to address this seeming contradiction, the objective of this study was to comprehensively investigate the effects of long-term (18 weeks) exposure of nicotine on tendon-to-bone microstructural properties in a rat model. We hypothesized that long term subcutaneous nicotine delivery would lead to diminished tendon mechanical properties, decreased bone microstructure in the humeral head, and altered tendon cell morphology compared to age-matched control rats receiving saline. Results demonstrated a small decrease in tendon size and stiffness, with decreased cell density in the tendon midsubstance. However, no differences were found in the enthesis fibrocartilage or in the underlying subchondral or trabecular bone. In conclusion, our study revealed limited effects of nicotine on the homeostatic condition of the supraspinatus tendon, enthesis, and underlying bone. Future studies are needed to ascertain effects of other components of tobacco products.

The effect of maternal HMB supplementation on bone mechanical and geometrical properties, as well as histomorphometry and immunolocalization of VEGF, TIMP2, MMP13, BMP2 in the bone and cartilage tissue of the humerus of their newborn piglets.

The presented experiment focuses on assessing the impact of HMB (hydroxy-ß-methobutyrate) supplementation of mothers during pregnancy on the development of the skeletal system of their offspring. For this purpose, an experiment was carried out on 12 clinically healthy sows of the Great White Poland breed, which were divided randomly into two groups the control and the HMB group. All animals were kept under standard conditions and received the same feed for pregnant females. In contrast, females from the HMB group between 70 and 90 days were supplemented with 3-hydroxy-3-methylbutyle in the amount of 0.2g/kg b.w/day. Immediately after birth, the piglets were also divided into groups based on: sex, and presence or lack HMB supplementation, and subsequently were euthanized and humerus bones from all piglets were collected. Mother's HMB supplementation during pregnancy affected the multiple index of their offspring. The higher humerus mass and length was observed with the greater effect in males. Maternal supplementation also influenced on the geometrical and mechanical properties of the humerus as in the case of mass, this effect was higher in males. Also, the collagen structure of the compacted and trabecular bone changed under the HMB addition. Maternal supplementation also affected the expression of selected proteins in growth cartilage and trabecular bone. The obtained results show that the administration to the mother during pregnancy by the HMB significantly affects the development of the humerus in many ways. The obtained results also confirm the utility of such experiments in understanding of the importance of the pregnancy diet as an develop and adaptable factor of offspring organisms and are the base for further research in that area as well as in the protein markers expression area.

The natural progression of shoulder osteonecrosis related to corticosteroid treatment.

BACKGROUND: Little is known about the rate and factors of progression of shoulder osteonecrosis (ON) related to corticosteroids. PURPOSE: We retrospectively evaluated 125 patients (215 shoulders) with humeral head ON diagnosed by MRI to determine the delay between corticosteroid treatment and the different stages and factors influencing the progression of the disease. METHODS: Seventy-four of the shoulders had asymptomatic Stage I ON, 58 had asymptomatic Stage II ON, 46 had symptomatic Stage I ON, and 37 had symptomatic Stage II ON. The minimum followup was 10 years (average, 14 years; range, 10-20 years). The delay between the beginning of the corticosteroid treatment and the diagnosis of ON of the humeral head averaged 15 months (range, 6-24 months). RESULTS: We observed partial or total regression on MRI only in patients with asymptomatic Stage I ON. At last followup, pain had developed in 98 (74%) and collapse had occurred in 71 (54%) of the 132 previously asymptomatic shoulders. Of the 83 symptomatic shoulders, 68 (82%) had collapsed at the final followup. The time between diagnosis and collapse averaged 10 years for patients with symptomatic Stage I ON and 3 years for patients with symptomatic Stage II ON. CONCLUSIONS: Stage at initial visit, occurrence of pain, and continuation of peak doses of corticosteroids predicted progression of disease in asymptomatic shoulders, whereas in the symptomatic shoulders, extent and location of the lesion were the main risk factors for progression. LEVEL OF EVIDENCE: Level II, prognostic study. See Guidelines for Authors for a complete description of levels.

The effect of soaking allograft in bisphosphonate: a pilot dose-response study.

BACKGROUND: Long-term survival of uncemented total joint replacements relies on osseointegration. With reduced bone stock impacted morselized allograft enhances early implant fixation but is subject to resorption. PURPOSE: We therefore asked whether soaking morselized allograft in different concentrations of bisphosphonate before impaction would enhance fixation. METHODS: In each of 10 dogs, we implanted four unloaded titanium implants surrounded by a 2.5-mm gap into the proximal humerus, two implants in each humerus. The gap was filled with impacted morselized allograft soaked in saline or a low-, middle-, or high-dose bisphosphonate solution (0.005, 0.05, or 0.5 mg zoledronate/mL). At 4 weeks, the implants were evaluated by histomorphometric analysis and mechanical pushout test. RESULTS: The low dose of zoledronate increased new bone formation in the allograft but the high dose decreased new bone formation. The high dose of zoledronate resulted in the greatest inhibition of allograft resorption, whereas the low dose of zoledronate resulted in the lowest inhibition of allograft resorption. Implants surrounded allograft soaked in the low dose of zoledronate or saline had better fixation for all three mechanical parameters compared with implants surrounded by allograft soaked in the middle or high dose of zoledronate. CONCLUSIONS: These data suggest bisphosphonate may enhance osseointegration of allografted implants and emphasize the need for preclinical testing of antiresorptive therapies.