Standard or Fin SIGN® nail? which option is better for the treatment of femoral fractures in low and middle-income countries?

PURPOSE: Femoral fractures are common in low and middle-income countries (LMIC), predominantly caused by high-energy trauma. The surgical implant generation network (SIGN®) program offers two different intramedullary nails in LMIC which are designed to be used without image intensifier free of charge for the patients: the SIGN standard nail (SSN®) and the SIGN Fin nail (SFN®). This study aimed to compare the results of the SSN® and the SFN® for the treatment of middle and distal shaft femoral fractures through a retrograde approach. MATERIAL AND METHODS: This was a retrospective, descriptive, and non-experimental study including all consecutive patients who underwent surgical management of middle or distal shaft femoral fracture between January 2017 and May 2022 in an NGO hospital located in Freetown, Sierra Leone. The duration of surgery, type of reduction, complications like screw loosening, implant migration, anterior knee pain and non-union rate at six months of follow up were evaluated. RESULTS: A total of 122 patients were included in the study. Group A: 60 patients were managed with SSN® and Group B: 62 patients with SFN®. The mean operative time was 104 min with SSN® and 78 with SFN® (p < 0.001). Open reduction of the fracture was necessary in ten (16.7%) patients with SSN® and 12 (19.4%) patients treated with SFN® (p = 0.69). Non-union was observed in one (1.7%) patient with SSN® and two (3.2%) patients with SFN® (p = 0.57). CONCLUSIONS: Both options seem equally effective in treating midshaft and distal femoral shaft fractures. The SFN® reduces the surgical time, due to this fact, in polytraumatized patients, patients with bilateral femur fracture or patients with ipsilateral tibia fracture, it can be considered as the best option to be used. There was no statistical difference in the complications presented by the two groups.

Contribution of the BioballTM head-neck adapter to the restoration of femoral offset in hip revision arthroplasty with retention of a well-fixed cup and stem.

PURPOSE: Failure to restore the femoral offset of the native hip is a potential cause of dysfunctional hip arthroplasty. The aim of this study was to report our experience of using a modular head-neck adapter in revision THA, specifically analyzing its usefulness as a tool to correct a slightly diminished femoral offset. MATERIALS AND METHODS: This was a retrospective single-center study including all hip revisions performed at our institution from January 2017 to March 2022 where the BioBallTM head-neck metal adapter was used. The preoperative and one year follow-up modified Merle d'Aubigné hip score was used to evaluate functional outcomes. RESULTS: Of a total of 34 cases included for revision, the head-neck adapter system was used specifically in six patients (17.6%) to increase femoral offset, retaining both the acetabular and femoral components. In this subgroup of patients, mean offset decrease after primary THA was 6.6 mm (4.0-9.1), equivalent to a mean 16.3% femoral offset reduction. The median modified Merle d'Aubigné score went from 13.3 preoperatively to 16.2 at one year follow-up. CONCLUSION: The use of a head-neck adapter is a safe and reliable procedure that may allow the surgeon to easily correct a slightly diminished femoral offset in a dysfunctional THA without the need to revise well-fixed prosthetic components.

Two novel prehabilitation apps to help patients stop smoking and risky drinking prior to hip and knee arthroplasty.

PURPOSE: Daily smoking or risky drinking increases the risk of complications after surgery by ~50%. Intensive prehabilitation aimed at complete cessation reduces the complication rate but is time-consuming. The purpose of this study was to carry out preoperative pilot tests (randomized design) of the feasibility (1A) and validation (1B) of two novel prehabilitation apps, habeat® (Ha-app) or rehaviour® (Re-app). METHODS: Patients scheduled for hip or knee arthroplasty with daily smoking, risky drinking, or both were randomised to one of the two apps. In part 1A, eight patients and their staff measured feasibility on a visual analog scale (VAS) and were interviewed about what worked well and the challenges requiring improvement. In part 1B, seven patients and their staff tested the improved apps for up to two weeks before validating the understanding, usability, coverage, and empowerment on a VAS and being interviewed. RESULTS: In 1A, all patients and staff returned scores of ≥5 for understanding the apps and mostly suggested technical improvements. In 1B, the scores varied widely for both apps, with no consensus achieved. Two of four patients (Ha-app) and one-third of the patients (Re-app) found the apps helpful for reducing smoking, but without successful quitting. The staff experienced low app competencies among patients and high time consumption. Specifically, patients most often needed help for the Ha-app, and the staff most often for Re-app; however, the staff reported the Re-app dashboard was more user-friendly. Support and follow-up from an addiction specialist staff member were suggested to complement the apps, thereby increasing the time consumption for staff. CONCLUSIONS: This pilot study to test prototype apps generated helpful feedback for the app developers. Based on the patient and staff comments, multiple improvements in functionality seem required before scaling up the evaluation for effect on prehabilitation and postoperative complications.

Can the intra-operative measurement of the diameter of the femoral head help surgeons to choose the best size of the acetabular cup?

PURPOSE: We hypothesized that the intra-operative measurement of the femoral head may increase the accuracy of the acetabular cup size optimal selection in total hip arthroplasty (THA). The purpose of this clinical research was to analyze the correlation between the estimated cup size from intra-operative measurement of the femoral head and the pre-operative templated cup size. METHODS: A prospective observational single-center study was conducted from June 2019 to January 2020 including primary THA (n = 100). All cases were pre-operatively templated. The measurement of the anterior-posterior diameter of the femoral head was routinely intra-operatively performed. Any definitive implanted cup was considered as "oversized" when the size was > 4 mm than the diameter of the native head. RESULTS: The median (interquartile range) size of the implanted cup, pre-operative planned cup size, and diameter of the femoral head were measured 52 (50-54) mm, 50 (48-54) mm and 49 (45-51) mm, respectively. Pre-operative planned size cup accurately predicted the implanted cup or differed in only one size (2 mm) in 77 (78%) cases. Otherwise, intra-operative femoral head measurement method accurately predicted the implanted or differed in only one size (2 mm) in 51 (87%) cases (p = 0.097). CONCLUSION: The intra-operative femoral head measurement is a simple and reliable tool to help the surgeons choose the best size of the acetabular cup and is as reliable as the pre-operative templating in order to avoid cup oversizing in THA. Utmost caution is warranted whenever the cup reamer is > 4 mm than the anterior-posterior diameter of the native head.

Safe drilling angles avoid femoral tunnel complications during combined anterolateral ligament and anterior cruciate ligament reconstruction.

PURPOSE: To determine the best angle to drill the femoral tunnels of an anterolateral ligament (ALL) anatomic reconstruction combined with a single-bundle anterior cruciate ligament (ACL) reconstruction to avoid tunnel collisions and cortical disruption. METHODS: Ten cadaveric knees were studied. Single-bundle anatomic ACL femoral tunnels were arthroscopically drilled. The starting point of the ALL femoral tunnel was located posterior and superior to the lateral epicondyle. ALL tunnels were drilled at four different angulations: (1) 0° axial/0° coronal, (2) 0° axial/30° coronal superior, (3) 30° axial anterior/0° coronal, and (4) 30° axial anterior 30° coronal superior. Specimens were scanned by computed tomography to measure the relations of each trajectory with the ACL socket and the nearest cortical bone. RESULTS: None of the four trajectories studied presented risk of collision with the ACL. The tunnel at 30° anterior/30° proximal presented the safest distance to the ACL socket (P = 0.01) [mean distance 18.6 mm (SD ± 6.7)]. However, both tunnels angled at 0° in the axial plane presented a high risk of posterior femoral cortex disruption (P = 0.01), either by close proximity or direct contact in some specimens (mean distance 3.1 mm (SD ± 2.8) at 0° axial/0° coronal and 3.7 mm (SD ± 2.2) at 0° axial/30° coronal). CONCLUSIONS: When performing simultaneous ACL and ALL ligament reconstruction, the ALL femoral tunnel should be drilled with an angle of 30° anterior in the axial plane and 30° proximal in the coronal plane. Tunnels with an angle of 0° in the axial plane showed high risk of contact and disruption of the posterior femoral cortex; thus, these angles should be avoided. The clinical relevance of this work is that an ALL anatomical reconstruction does not represent a risk when performing a simultaneous ACL reconstruction as long as the ALL tunnel is reamed with a proximal and anterior angulation.

Early clinical and radiological outcomes for the Taperloc Complete Microplasty stem.

The use of short stem designs in total hip arthroplasty is not a new concept, but its popularity has increased as a bone-sparing alternative to traditional stems. This study analyzed the midterm clinical and radiological results of the Taperloc Complete Microplasty stem (Zimmer Biomet® Warsaw, IN, USA). A total of 32 patients (20 men and 12 women) were retrospectively documented and received 40 stems (eight bilateral). The median patient age was 50 years (interquartile range 43-58) at the time of surgery. The median follow-up was 36.5 months (interquartile range 26.75-50.25). Indication for total hip arthroplasty was osteoarthritis (62.5% of patients), avascular necrosis (25%), and developmental dysplasia of the hip (12.5%). The Merle d'Aubigné score improved from a mean 11.5 preoperatively to a mean 17.5 at the latest follow-up. During X-ray assessment, we observed one subsidence of the stem (3 mm) and four cases of varus malalignment without clinical consequences. No cases of osteolysis were reported, and no stems were revised. According to our results, this short tapered stem shows a good early-term outcome. Prospective results and a longer follow-up are needed to assess the long-term survival of this stem fully.

Ursodeoxycholic acid decreases bilirubin-induced osteoblast apoptosis.

BACKGROUND: Low bone turnover osteoporosis is common in cholestatic diseases. Ursodeoxycholic acid (UDCA) counteracts the damaging effects of bilirubin or lithocholic acid (LCA) on osteoblast viability, proliferation and mineralisation. UDCA is anti-apoptotic in various cell lines, but this effect in bone cells is unknown. Therefore, the consequences of bilirubin and LCA on apoptosis, and whether UDCA has anti-apoptotic effects have been assessed on osteoblasts. MATERIALS AND METHODS: Human osteoblasts (hOB) and osteosarcoma cell line (Saos-2) were treated with camptothecin as a pro-apoptotic agent, and UDCA, LCA and bilirubin. Apoptosis was determined by DNA fragmentation, flow cytometry, caspase-3 activity and expression of pro-apoptotic (Bcl-2-associated X protein BAX) and anti-apoptotic (BCL2 and BCL2-like 1 protein, BCL2L) genes. RESULTS: Both LCA (10 µM) and bilirubin (50 µM) induced apoptosis as indicated by DNA fragmentation (4·7- and 3·7-fold, respectively, P < 0·001), caspase-3 activity and flow cytometry in Saos-2 and hOB. UDCA (10 µM) reduced the apoptotic effects of camptothecin (0·5 µM) by 61%, (P < 0·001) and counteracted the apoptotic effects of LCA and bilirubin determined by DNA fragmentation (56% and 60%, respectively, P < 0·001), cytometry and caspase-3 activity in Saos-2, with lower effects in hOB. UDCA (10 µM) downregulated BAX (75%), upregulated BCL2L (10-fold, P < 0·01) genes, and neutralised BAX upregulation (P < 0·01) and BCL2L downregulation (P < 0·01) induced by LCA and bilirubin. CONCLUSIONS: Bilirubin and LCA induce apoptosis in osteoblastic cells. UDCA counteracts the apoptotic consequences of these two substances, and therefore, it may have further beneficial effects on the decreased bone formation in the cholestasis.

Treatment Options for Failed Back Surgery Syndrome: An Umbrella Systematic Review of Systematic Reviews on the Effectiveness of Therapeutic Interventions.

Background: Failed back surgery syndrome (FBSS) is a common and incapacitating condition affecting patients with previous spine surgery in whom treatment approach can be challenging. This study aimed to summarize existing secondary studies and up-to-date randomized clinical trials (RCTs) that assess the effectiveness of available treatment options for FBSS. Methods: Systematic searches were carried out in five databases (PubMed, Cochrane, Scielo, Epistemonikos, and Google scholar) for all systematic reviews on the effectiveness of treatment options for FBSS published after 2012. Outcomes of interest were pain levels measured through visual analog scale or numeric rating scale, Oswestry Disability Index, and quality of life. Methodological and risk of bias assessments were performed with the AMSTAR-2 tool for systematic reviews and the Joanna Briggs Institute checklist for RCT. Prospective PROSPERO registration: CRD42022307609. Results: Fifteen studies, seven systematic reviews, and eight RCTs met the inclusion criteria and fulfilled the methodological quality assessment. Of the 15 included studies, 8 were on neurostimulation, 4 on adhesiolysis, 4 on epidural or intrathecal injections, and 3 on other treatment modalities. The risk of bias was low in seven studies, moderate in five, and high in three. Conclusions: Based on this systematic overview and the considerable heterogeneity among studies, the FBSS therapeutic approach must be individualized. FBSS treatment should start with conservative management, considering the implementation of neurostimulation, a technique with the most robust evidence of effective results, in cases of refractory axial or neuropathic pain. As the last resource, in light of the evidence found, more invasive procedures or new surgical interventions are indicated.

Ursodeoxycholic acid increases differentiation and mineralization and neutralizes the damaging effects of bilirubin on osteoblastic cells.

BACKGROUND: Osteoporosis resulting from decreased bone formation is a common complication in patients with chronic cholestasis. Lithocholic acid (LCA) and bilirubin may play a role in osteoporosis given that both substances have detrimental effects on survival of human osteoblasts, the cells involved in bone formation. AIMS: As ursodeoxycholic acid (UDCA) improves cholestasis, we have assessed if this bile acid may neutralize the harmful effects of LCA, bilirubin and sera from jaundiced patients on osteoblastic cells. METHODS: The experiments were performed in primary human osteoblasts and human osteosarcoma cell line (Saos-2) at different times and concentrations of UDCA, LCA, cholic acid (CA), bilirubin and sera from jaundiced patients to assess cell viability, differentiation and mineralization. RESULTS: UDCA significantly decreased cell survival at concentrations 10 times higher (1 mM) than that observed with LCA, whereas CA did not decrease osteoblast survival. UDCA (100 µM) neutralized the damaging effects of bilirubin (50 µM) and sera from jaundiced patients on survival. Moreover, UDCA (1 µM and 10 µM) increased osteoblast differentiation in cells treated with harmful concentrations of LCA or bilirubin. UDCA (100 µM) increased cell differentiation in osteoblasts cultured with a mix of serum from cholestatic patients by 23%. Furthermore, UDCA increased osteoblast mineralization by 35% and neutralized the negative consequences of 50 µM bilirubin. CONCLUSIONS: UDCA increases osteoblast differentiation and mineralization, and neutralizes the detrimental effects of lithocholic acid, bilirubin and sera from jaundiced patients on osteoblastic cells. Therefore, UDCA may exert a favourable effect on bone in patients which chronic cholestasis.

Virtual embodiment for improving range of motion in patients with movement-related shoulder pain: an experimental study.

BACKGROUND: Recent evidence supports the use of immersive virtual reality (VR) as a means of delivering bodily illusions that may have therapeutic potential for the treatment of musculoskeletal conditions. We wanted to investigate whether a single session of an embodiment-based immersive VR training program influences pain-free range of motion in patients with shoulder pain. METHODS: We designed a rehabilitation program based on developing ownership over a virtual body and then "exercising" the upper limb in immersive VR, while the real arm remains static. We then carried out a single-arm pre-post experiment in which 21 patients with movement-related musculoskeletal shoulder pain were exposed to the 15-min VR program and measured their active pain-free range of motion immediately before and afterwards. RESULTS: We found that shoulder abduction and hand-behind-back movements, but not shoulder flexion, were significantly and clinically improved post-intervention and that the level of improvement correlated with the level of embodiment. Following this one session, at 1-week follow-up the improvements were not maintained. CONCLUSIONS: Virtual embodiment may be a useful therapeutic tool to help improve range of motion in patients with movement-related shoulder pain in the short term, which in turn could expedite rehabilitation and recovery in these conditions.

Effects of bilirubin and sera from jaundiced patients on osteoblasts: contribution to the development of osteoporosis in liver diseases.

UNLABELLED: Low bone formation is considered to be the main feature in osteoporosis associated with cholestatic and end-stage liver diseases, although the consequences of retained substances in chronic cholestasis on bone cells have scarcely been studied. Therefore, we analyzed the effects of bilirubin and serum from jaundiced patients on viability, differentiation, mineralization, and gene expression in the cells involved in bone formation. The experiments were performed in human primary osteoblasts and SAOS-2 human osteosarcoma cells. Unconjugated bilirubin or serum from jaundiced patients resulted in a dose-dependent decrease in osteoblast viability. Concentrations of bilirubin or jaundiced serum without effects on cell survival significantly diminished osteoblast differentiation. Mineralization was significantly reduced by exposure to 50 µM bilirubin at all time points (from -32% to -55%) and jaundiced sera resulted in a significant decrease on cell mineralization as well. Furthermore, bilirubin down-regulated RUNX2 (runt-related transcription factor 2) gene expression, a basic osteogenic factor involved in osteoblast differentiation, and serum from jaundiced patients significantly up-regulated the RANKL/OPG (receptor activator of nuclear factor-κB ligand/osteoprotegerin) gene expression ratio, a system closely involved in osteoblast-induced osteoclastogenesis. CONCLUSION: Besides decreased cell viability, unconjugated bilirubin and serum from jaundiced patients led to defective consequences on osteoblasts. Moreover, jaundiced serum up-regulates the system involved in osteoblast-induced osteoclastogenesis. These results support the deleterious consequences of increased bilirubin in advanced chronic cholestasis and in end-stage liver diseases, resulting in disturbed bone formation related to osteoblast dysfunction.

Recurrent Cervical Subdural Bleeding Because of Atlantoaxial Instability in a Patient with Rheumatoid Arthritis: A Case Report.

CASE: Atlantoaxial instability (AAI) is a frequent complication of rheumatoid arthritis (RA), but its involvement in intracranial bleeding is unclear. We present a young woman with history of systemic lupus erythematosus and RA who developed 3 episodes of subdural bleeding at the upper cervical spine and cranial level. Imaging tests showed signs of AAI with odontoid deformity. The case was interpreted as recurrent traumatic cervical subdural hemorrhage because of AAI. No new episodes occurred after surgical C1-C2 fixation. CONCLUSION: We report a case that had the association of hemorrhage and C1-2 instability in a patient with RA and lupus erythematosus.

A lower starting point for the medial cut increases the posterior slope in opening-wedge high tibial osteotomy: a cadaveric study.

PURPOSE: The objective of this study was to evaluate the effects on the posterior tibial slope of different distances from the joint line to start the osteotomy and of varying the placement of the opening wedge in high tibial osteotomy. Starting the osteotomy more distally and an incorrect location for the tibial opening wedge were hypothesized to increase the posterior tibial slope. METHODS: A cadaveric study was conducted using 12 knees divided into two groups based on the distance from the joint line to the start of the osteotomy: 3 and 4 cm. The preintervention posterior tibial slope was measured radiologically. Once the osteotomy was performed, the medial cortex of the tibia was divided into anteromedial, medial, and posteromedial thirds. A 10° opening wedge was sequentially placed in each third, and the effect on the posterior tibial slope was evaluated radiographically. RESULTS: Significant changes were observed only in the 3-cm group (p = 0.02) when the wedge was placed in the anteromedial zone. In contrast, in the 4-cm group, significant differences were observed when the opening wedge was placed at both the medial (p = 0.04) and anteromedial (p = 0.012) zones. CONCLUSION: Correct control of the posterior tibial slope can be achieved by avoiding a low point when beginning the osteotomy and placing the opening wedge in the posteromedial third of the tibia when performing an opening-wedge high tibial osteotomy. LEVEL OF EVIDENCE: Controlled laboratory study.

Clinical and Radiological Outcome in a Series of Patients Treated by Anterior Cervical Discectomy and Fusion: Retrospective Controlled Study With 2 Different Stand-Alone Cages.

BACKGROUND: Cervical spine balance and alignment targets after cervical spine surgery are poorly established in patients with cervical spine degenerative disease surgically treated by anterior cervical discectomy and fusion (ACDF). The objective of the study is to determine the correlation between radiological and clinical outcomes in patients surgically treated by ACDF with 2 different stand-alone cervical cages. METHODS: Clinical outcomes were evaluated using visual analog scale (VAS), Neck Disability Index (NDI), Nurick Scale, and Japanese Orthopedic Association score for myelopathy. Radiological evaluation included cervical and segmental Cobb angles, cervical sagittal vertical axis (cSVA), T1 slope (T1s), C0-C2 angle, fusion rates, adjacent segment degeneration, and cage subsidence. RESULTS: A total of 80 patients were included with an average age of 53 years. There was a statistically significant improvement in both clinical and radiological evaluations. There was a statistical significant correlation between cervical pain on cervical VAS and cSVA. There was a significant correlation between postoperative T1s and cSVA, related to the improvement in cervical angles. There was no significant difference in rates of fusion, adjacent segment changes, or reoperation between both cervical cages, and there was a higher rate of subsidence in the Aleutian group. There were significant differences between both groups on postoperative NDI and VAS, but this difference is not maintained during follow-up. CONCLUSIONS: Cervical sagittal balance is directly related to clinical outcome in patients with cervical spine degenerative disease. Both cervical implants analyzed were comparable in clinical and radiological outcomes. CLINICAL RELEVANCE: There are important clinical and radiological parameters that should be taken into account for the analysis of the surgical outcome of patients treated by ACDF; this is one of the few studies that report the results with 2 different cervical cage designs.

Local recurrence of a parosteal osteosarcoma 21 years after incomplete resection.

Parosteal osteosarcoma (POS) is the most common form of surface osteosarcoma. Its symptoms are insidious and its duration prior to diagnosis is considerably longer than that of other types of osteosarcoma. We report a case of POS with a growing mass but no evidence of metastasis. This tumor, which was diagnosed as calcified hematoma with benign characteristics, was incompletely resected in our hospital 21 years before the diagnosis of recurrence. The patient underwent a wide en bloc resection in our hospital and was free of symptoms, with no signs of tumor recurrence or metastasis during a 53-month follow-up.

Myositis ossificans mimicking parosteal osteosarcoma: a case report and literature review.

Myossitis ossificans (MO) is an aberrant reparative process that causes benign heterotopic ossification in soft tissue. We report a case of MO presenting as a large mass located at the dorsal aspect of the distal thigh, with no history of trauma, with radiological and clinical features mimicking parosteal sarcoma. An incisional biopsy was performed and the mass was excised. The histological features identified the lesion as MO. In half of the cases, these ossifications may adhere to the periosteum. In these cases, the lesion is known as parosteal MO, which may be confused with a parosteal osteosarcoma. This parosteal MO seldom becomes malignant. We emphasize the importance of a differential diagnosis of MO, since these lesions may simulate tumours and lead to misdiagnosis.

Necrotizing fasciitis: Usefulness of the LRINEC score in a third-level hospital.

AIM: To review patients seen in the emergency room, diagnosed with necrotizing fasciitis (NF) and the correlation of such complications with the Laboratory Risk Indicator for Necrotizing fasciitis scale (LRINEC). The purpose of this study is to assess the use of the LRINEC score for early diagnosis of NF and its prognostic use in a consecutive series of cases treated at our hospital. METHODS: Retrospective observational study including patients with a diagnosis of NF in the emergency room of a tertiary hospital over 11 years. The results are shown as median, interquartile range and absolute range for quantitative variables. In the case of qualitative variables, the results are shown as absolute and relative frequency. The comparison between the categories of the LRINEC scale was performed through a post-hoc comparison from a non-parametric rank-ANOVA analysis. Comparisons between LRINEC groups in the qualitative variables were performed using Fisher's exact test. RESULTS: A total of 45 patients with a mean age of 51 years were identified. There was a 20% mortality rate (9 cases). The highest mortality rate was registered in the high-risk group (LRINEC greater than 8) with 4 deceased individuals (44.44%), while in the low and moderate-risk groups, 3 and 2 deceased individuals (33% and 22%) were registered, respectively, without considering this result statistically significant (p=0.811). There was an amputation rate of 15.6% (7 cases). The average LRINEC score was greater in the cases that required amputation 9 (95% CI 7; 13) in comparison to the other patients, 6 (95% CI 5; 8), p=0.044. The average hospital stay lasted 32.5 days (95% CI: 25; 40); 30 days in the low-risk group, 41 days in the moderate-risk group and 40 days in the high-risk group. Mortality was associated to a smaller number of interventions (p=0.005) and was preceded by septic shock in all cases. CONCLUSIONS: The LRINEC score may be useful to aid diagnosis. However, clinical suspicion is the most important in diagnosis. A LRINEC low score does not exclude NF. In this retrospective series, 35.71% of cases presented a low LRINEC score, making the rate of false negatives high. In view of these results, The LRINEC score cannot be used as a prognostic value since an initial low score does not rule out serious evolution.

Bile acids and bilirubin effects on osteoblastic gene profile. Implications in the pathogenesis of osteoporosis in liver diseases.

Osteoporosis in advanced cholestatic and end-stage liver disease is related to low bone formation. Previous studies have demonstrated the deleterious consequences of lithocholic acid (LCA) and bilirubin on osteoblastic cells. These effects are partially or completely neutralized by ursodeoxycholic acid (UDCA). We have assessed the differential gene expression of osteoblastic cells under different culture conditions. The experiments were performed in human osteosarcoma cells (Saos-2) cultured with LCA (10 µM), bilirubin (50 µM) or UDCA (10 and 100 µM) at 2 and 24 h. Expression of 87 genes related to bone metabolism and other signalling pathways were assessed by TaqMan micro fluidic cards. Several genes were up-regulated by LCA, most of them pro-apoptotic (BAX, BCL10, BCL2L13, BCL2L14), but also MGP (matrix Gla protein), BGLAP (osteocalcin), SPP1 (osteopontin) and CYP24A1, and down-regulated bone morphogenic protein genes (BMP3 and BMP4) and DKK1 (Dickkopf-related protein 1). Parallel effects were observed with bilirubin, which up-regulated apoptotic genes and CSF2 (colony-stimulating factor 2) and down-regulated antiapoptotic genes (BCL2 and BCL2L1), BMP3, BMP4 and RUNX2. UDCA 100 µM had specific consequences since differential expression was observed, up-regulating BMP2, BMP4, BMP7, CALCR (calcitonin receptor), SPOCK3 (osteonectin), BGLAP (osteocalcin) and SPP1 (osteopontin), and down-regulating pro-apoptotic genes. Furthermore, most of the differential expression changes induced by both LCA and bilirubin were partially or completely neutralized by UDCA. Conclusion: Our observations reveal novel target genes, whose regulation by retained substances of cholestasis may provide additional insights into the pathogenesis of osteoporosis in cholestatic and end-stage liver diseases.