Stem Cells and Their Derivatives: An Implication for the Regeneration of Nonunion Fractures.

Despite advances in biomedical research, fracture nonunion rates have remained stable throughout the years. Long-bone fractures have a high likelihood of nonunion, but the specific biological pathways involved in this severe consequence are unknown. Fractures often heal in an organized sequence, including the production of a hematoma and an early stage of inflammation, the development of a soft callus and hard callus, and eventually the stage of bone remodeling. Deficient healing can result in a persistent bone defect with instability, discomfort, and loss of function. In the treatment of nonunions, mesenchymal stem cells (MSCs) prove to be a promising and safe alternative to the standard therapeutic strategies. Moreover, novel scaffolds are being created in order to use a synergistic biomimetic technique to rapidly generate bone tissue. MSCs respond to acellular biomimetic matrices by regenerating bone. Extracellular vesicles (EVs) derived from MSCs have recently gained interest in the field of musculoskeletal regeneration. Although many of these techniques and technologies are still in the preclinical stage and have not yet been approved for use in humans, novel approaches to accelerate bone healing via MSCs and/or MSC derivatives have the potential to reduce the physical, economic, and social burdens associated with nonhealing fractures and bone defects. In this review, we focus on providing an up-to-date summary of recent scientific studies dealing with the treatment of nonunion fractures in clinical and preclinical settings employing MSC-based therapeutic techniques.

A multimodal opioid-sparing pain management following total knee replacement.

OBJECTIVE: The purpose of this study is to compare the pain scores, opioid consumption, and range of motion of the operated knee after total knee replacement (TKR) in the 10-day follow-up period between a traditional opioid-containing pain management protocol and a multimodal opioid-sparing treatment protocol. METHODS: This prospective, randomized, single-center study included 90 patients (24 men and 66 women; mean age 69.7±7.2 years) undergoing TKR for osteoarthritis between October 2019 and October 2020. Patients were randomized into 3 cohorts for comparison: traditional opioid-containing pain management protocol (n=30), multimodal opioid-sparing pain management protocol (n=30), and traditional opioid-containing pain management protocol with additional local infiltration analgesia (LIA). Changes in visual analog scale for pain (VAS), range of motion (ROM), and opioid consumption were compared between groups. RESULTS: A lower mean postoperative VAS score was observed in the opioid-sparing cohort, which was statistically significant at all time points compared with the traditional cohorts. Mean total morphine consumption was significantly lower in the opioid-sparing cohort (2.7±5.8 MMEs) compared to the traditional (14.0±14.8 MMEs) and traditional with LIA cohorts (8.3±9.5 MMEs; p<0.05). The mean degree of flexion of the operated knee of patients was significantly greater in patients in the opioid-sparing group than in the other groups on the postoperative day 3 (opioid-sparing: 87.0±11.2°; traditional: 74.1±11.6°; traditional with LIA: 84.7±8.9°; p<0.05), as well as on day 10 (opioid-sparing: 99.3±10.8°; traditional: 87.3±12.4°; traditional with LIA: 92.5±9.7°; p<0.05). The rate of adverse events after TKR did not differ between the groups. CONCLUSION: The results of this study suggest that a multimodal opioid-sparing pain protocol after TKR, which includes oral non-opioid medications and periarticular injection with bupivacaine, provides better pain relief and early functional gains with fewer rescue opioids compared to traditional opioid-based protocols (Tab. 4, Fig. 2, Ref. 22).

Association Analysis of GDF5 and Contributing Factors in Developmental Dysplasia of the Hip in Infants.

BACKGROUND: Developmental dysplasia of the hip (DDH) is a developmental disorder which is reported to be associated with hip instability. When untreated, it can lead to irreversible joint damage. DDH is known to be a multifactorial disease involving genetic, mechanical and environmental factors. The greatest causative potential is attributed to the genetic component. Growth Differentiation Factor 5 (GDF5) is among the most studied genes associated with processes of regeneration and maintenance of joints. The aim of this work was to analyse the association of SNP rs143383 in the GDF5 gene and the occurrence of DDH, along with association with various contributing factors in the Caucasian population. MATERIAL AND METHODS: A total of 118 samples were analysed for the presence of the mutation. DNA was isolated from all individuals from peripheral blood. SNP rs143383 in the GDF5 gene was genotyped using the TaqMan assay. A standard chi-square test was used to compare allele and genotype distributions in patients and healthy controls. RESULTS: The association analysis of genotypes of DDH and rs143383 revealed a significant association. Also, the association of GDF5 and selected contributing factors was statistically significant in female gender (p=0.002), family history (p<0.001), count of pregnancy (p=0.009), laterality of hip involvement and initial US examination. CONCLUSIONS: 1. The results indicate an important effect of rs143383 polymorphism in the GDF5 gene on DDH development. 2. However, our results also suggest that rs143383 is not the only contributing factor in the genetic component of DDH.

Stem Cells and Their Derivatives-Implications for Alveolar Bone Regeneration: A Comprehensive Review.

Oral and craniofacial bone defects caused by congenital disease or trauma are widespread. In the case of severe alveolar bone defect, autologous bone grafting has been considered a "gold standard"; however, the procedure has several disadvantages, including limited supply, resorption, donor site morbidity, deformity, infection, and bone graft rejection. In the last few decades, bone tissue engineering combined with stem cell-based therapy may represent a possible alternative to current bone augmentation techniques. The number of studies investigating different cell-based bone tissue engineering methods to reconstruct alveolar bone damage is rapidly rising. As an interdisciplinary field, bone tissue engineering combines the use of osteogenic cells (stem cells/progenitor cells), bioactive molecules, and biocompatible scaffolds, whereas stem cells play a pivotal role. Therefore, our work highlights the osteogenic potential of various dental tissue-derived stem cells and induced pluripotent stem cells (iPSCs), the progress in differentiation techniques of iPSCs into osteoprogenitor cells, and the efforts that have been made to fabricate the most suitable and biocompatible scaffold material with osteoinductive properties for successful bone graft generation. Moreover, we discuss the application of stem cell-derived exosomes as a compelling new form of "stem-cell free" therapy.

Genetic Study of IL6, GDF5 and PAPPA2 in Association with Developmental Dysplasia of the Hip.

BACKGROUND: Developmental dysplasia of the hip (DDH) is one of the most prevalent skeletal disorders. DDH is considered a pathologic condition with polygenic background, but environmental and mechanic factors significantly contribute to its multifactorial etiology. Inheritance consistent with autosomal dominant type has also been observed. Single-nucleotide polymorphisms (SNPs) in various genes mostly related to formation of connective tissue are studied for a possible association with DDH. METHODS: We genotyped three SNPs, rs1800796 located in the promoter region of the IL6 gene, rs143383 located in the 5' untranslated region (UTR) of the GDF5 gene and rs726252 located in the fifth intron of the PAPPA2 gene. The study consisted of 45 subjects with DDH and 85 controls from all regions of Slovakia. RESULTS: Association between DDH occurrence and studied genotypes affected by aforementioned polymorphisms was confirmed in the case of rs143383 in the GDF5 gene (p = 0.047), where the T allele was over-expressed in the study group. Meanwhile, in the matter of IL6 and PAPPA2, we found no association with DDH (p = 0.363 and p = 0.478, respectively). CONCLUSIONS: These results suggest that there is an association between DDH and GDF5 polymorphisms and that the T allele is more frequently presents in patients suffering from DDH.

iPSCs in Modeling and Therapy of Osteoarthritis.

Osteoarthritis (OA) belongs to chronic degenerative disorders and is often a leading cause of disability in elderly patients. Typically, OA is manifested by articular cartilage erosion, pain, stiffness, and crepitus. Currently, the treatment options are limited, relying mostly on pharmacological therapy, which is often related to numerous complications. The proper management of the disease is challenging because of the poor regenerative capacity of articular cartilage. During the last decade, cell-based approaches such as implantation of autologous chondrocytes or mesenchymal stem cells (MSCs) have shown promising results. However, the mentioned techniques face their hurdles (cell harvesting, low proliferation capacity). The invention of induced pluripotent stem cells (iPSCs) has created new opportunities to increase the efficacy of the cartilage healing process. iPSCs may represent an unlimited source of chondrocytes derived from a patient's somatic cells, circumventing ethical and immunological issues. Aside from the regenerative potential of iPSCs, stem cell-derived cartilage tissue models could be a useful tool for studying the pathological process of OA. In our recent article, we reviewed the progress in chondrocyte differentiation techniques, disease modeling, and the current status of iPSC-based regenerative therapy of OA.

Genetics of developmental dysplasia of the hip.

In the last decade, the advances in the molecular analyses and sequencing techniques allowed researchers to study developmental dysplasia of the hip (DDH) more thoroughly. Certain chromosomes, genes, loci and polymorphisms are being associated with variable severity of this disorder. The wide range of signs and symptoms is dependent either on isolated or systemic manifestation. Phenotypes of isolated cases range from only a mild ligamental laxity, through subluxation, to a complete dislocation of the femoral head. Systemic manifestation is connected to various forms of skeletal dysplasia and other malformations characterized by significant genetic aberrations. To reveal the background of DDH heredity, multiple studies focused on large sample sizes with an emphasis on the correlation between genotype, phenotype and continuous clinical examination. Etiological risk factors that have been observed and documented in patients include genetic, environmental, and mechanical factors, which significantly contribute to the familial or nonfamilial occurrence and phenotypic variability of this disorder. Still, the multifactorial etiology and pathogenesis of DDH are not yet sufficiently clarified, explained, or understood. Formation of connective tissue, osteogenesis, chondrogenesis, and all other affected pathways and variations in the function of their individual elements contribute to the creation of the pathology in a developing human body. This review article presents an up-to-date list of known DDH associated genes, their products, and functional characteristics.

Developmental Dysplasia of the Hip: A Review of Etiopathogenesis, Risk Factors, and Genetic Aspects.

As one of the most frequent skeletal anomalies, developmental dysplasia of the hip (DDH) is characterized by a considerable range of pathology, from minor laxity of ligaments in the hip joint to complete luxation. Multifactorial etiology, of which the candidate genes have been studied the most, poses a challenge in understanding this disorder. Candidate gene association studies (CGASs) along with genome-wide association studies (GWASs) and genome-wide linkage analyses (GWLAs) have found numerous genes and loci with susceptible DDH association. Studies put major importance on candidate genes associated with the formation of connective tissue (COL1A1), osteogenesis (PAPPA2, GDF5), chondrogenesis (UQCC1, ASPN) and cell growth, proliferation and differentiation (TGFB1). Recent studies show that epigenetic factors, such as DNA methylation affect gene expression and therefore could play an important role in DDH pathogenesis. This paper reviews all existing risk factors affecting DDH incidence, along with candidate genes associated with genetic or epigenetic etiology of DDH in various studies.

Surgical Techniques for Knee Cartilage Repair: An Updated Large-Scale Systematic Review and Network Meta-analysis of Randomized Controlled Trials.

PURPOSE: The aim of this study was to investigate the most appropriate surgical interventions for patients with knee articular cartilage defects from the level I randomized clinical trials. METHODS: We searched five databases for level I randomized clinical trials. Treatments were compared if reported in more than one study using network meta-analysis to boost the number of included studies per comparison. RESULTS: We studied 21 articles that included 891 patients. Traumatic lesion was the most common cause in the included patients. There were significantly higher failure rates in the microfracture (MF) group compared to autologous chondrocyte implantation (ACI) group at 10-year follow-up. Moreover, osteochondral autograft transplantation (OAT) showed significantly more excellent or good results at > 3-year follow-up compared to MF, whereas MF showed significantly more poor results versus ACI and matrix-induced autologous chondrocyte implantation (MACI). Furthermore, OAT showed significantly more poor results than MACI at 1-year follow-up. Similarly, patients who underwent OAT had higher return-to-activity rates than those with MF. It is noteworthy that the Knee injury and Osteoarthritis Outcome Score was higher in patients who underwent characterized chondrocyte implantation or MACI compared to MF. Finally, there were no significant differences among the various interventions regarding reintervention, biopsy types or adverse events. According to the P scores for interventions ranking, there was a disagreement concerning the best intervention; however, MF was always ranked as the last. CONCLUSIONS: Cartilage repair techniques, rather than MF, provide higher quality repair of tissue and have lower failure and higher return-to-activity rates. Moreover, OAT had significantly more excellent or good results compared to MF, whereas MF had significantly more poor results than ACI and MACI. Future studies need to have longer follow-up periods and more representative populations to investigate the efficacy and safety of these interventions. LEVEL OF EVIDENCE: Level I: meta-analysis of Level I studies.

Recent Progress in the Regeneration of Spinal Cord Injuries by Induced Pluripotent Stem Cells.

Regeneration of injuries occurring in the central nervous system, particularly spinal cord injuries (SCIs), is extremely difficult. The complex pathological events following a SCI often restrict regeneration of nervous tissue at the injury site and frequently lead to irreversible loss of motor and sensory function. Neural stem/progenitor cells (NSCs/NPCs) possess neuroregenerative and neuroprotective features, and transplantation of such cells into the site of damaged tissue is a promising stem cell-based therapy for SCI. However, NSC/NPCs have mostly been induced from embryonic stem cells or fetal tissue, leading to ethical concerns. The pioneering work of Yamanaka and colleagues gave rise to the technology to induce pluripotent stem cells (iPSCs) from somatic cells, overcoming these ethical issues. The advent of iPSCs technology has meant significant progress in the therapy of neurodegenerative disease and nerve tissue damage. A number of published studies have described the successful differentiation of NSCs/NPCs from iPSCs and their subsequent engraftment into SCI animal models, followed by functional recovery of injury. The aim of this present review is to summarize various iPSC- NPCs differentiation methods, SCI modelling, and the current status of possible iPSC- NPCs- based therapy of SCI.

Developmental Dysplasia of Hip: Perspectives in Genetic Screening.

Development dysplasia of the hip (DDH) is a complex developmental disorder despite being a relatively common condition mainly caused by incompatibility of the femoral head and the abnormal joint socket. Development dysplasia of the hip describes a wide spectrum of disorders ranging from minor acetabular dysplasia to irreducible dislocation of the hip. Modern medicine still suffers from lack of information about screening and precise genetic examination. Genome wide linkage and association studies have brought significant progress to DDH diagnosis. Association studies managed to identify many candidate (susceptible) genes, such as PAPPA2, COL2A1, HOXD9, GDF-5, and TGFB1, which play a considerable role in the pathogenesis of DDH. Early detection of DDH has a big chance to help in preventing further disability and improve the psychological health and quality of life in those children. This emphasizes the importance to establish a universal screening program along with the genetic counseling.

Identification of Prognostic and Predictive Osteosarcoma Biomarkers.

Both adolescents and children suffer from osteosarcoma, localized in the metaphysis of the long bones. This is the most common primary high-grade bone tumor in this patient group. Early tumor detection is the key to ensuring effective treatment. Improved osteosarcoma outcomes in clinical trials have been contingent on biomarker discovery and an evolving understanding of molecules and their complex interactions. In this review, we present a short overview of biomarkers for osteosarcoma, and highlight advances in osteosarcoma-related biomarker research. Many studies show that several biomarkers undergo critical changes with osteosarcoma progression. Growing knowledge about osteosarcoma-related markers is expected to positively impact the development of therapeutics for osteosarcoma, and ultimately of clinical care. It has also become important to develop new biomarkers, which can identify vulnerable patients who should be treated with more intensive and aggressive therapy after diagnosis.

Adolescent Idiopathic Scoliosis - Future Molecular-Based Diagnostic and Prognostic Testing.

Adolescent idiopathic scoliosis (AIS) is a three-dimensional deformity of the spine mainly affecting the younger population. Earlier detection of the disorder leads to appropriate treatment and better outcomes, thus avoiding highly invasive surgical treatments. The currently available tests for the disease identification have lost their reliability and validity with time. In the past few decades, efforts have been directed towards developing a highly reliable prognostic test for AIS. Towards this end, several strategies have been employed including biochemical, biomechanical and gene-based tests. Among the three, the gene-based technology has received much attention in recent past. Notably, this is due to the fact that the human genome project, followed by genome-wide association studies (GWAS), facilitated the identification of candidate genes for disorders like AIS. Several promising biomarker genes have been identified. However, their global validations were disappointing as these genes were shown to be limited to a particular group of people/ethnicities. Such observations limit the development of a reliable global molecular/biochemical test for AIS. The currently used AIS ScoliScoreTM also has several limitations. With continued disappointments in the identification of biomarkers for AIS and lack of appropriate tests, researchers have diverted their efforts towards several alternative avenues. A ray of hope is emerging from recent observations on the association of non-coding microRNAs and epigenetic factors that might arise as future reliable markers for AIS, thus paving the way for appropriate clinical management of this disorder.

Regenerative Medicine in Orthopaedics and Trauma: Challenges, Regulation and Ethical Issues.

The ability of stem cells to self-renew and differentiate into cell types of different lineages forms the basis of regenerative medicine, which focuses on repairing or regenerating damaged or diseased tissues. This has a huge potential to revolutionize medicine. It is anticipated that in future, stem cell therapy will be able to restore function in all major organs. Intensive research has been on-going to bring stem cell therapy from bench to bedside as it holds promise of widespread applications in different areas of medicine. This is also applicable to orthopaedics, where stem cell transplantation could benefit complications like spinal cord injury, critical bone defects, cartilage repair or degenerative disc disorders. Stem cell therapy has a potential to change the field of orthopaedics from surgical replacements and reconstructions to a field of regeneration and prevention. This article summarizes advances in stem cell applications in orthopaedics as well as discussing regulation and ethical issues related to the use of stem cells.

Operative treatment algorithm for intra-articular calcaneal fractures.

Displaced calcaneus fracture often results in severe permanent sequelae and considerably limits the activities of daily living. In this prospective cohort study we present the outcomes of surgical treatment of 137 displaced intra-articular calcaneal fractures, over 8y period. Follow-up data were obtained up to 3 years post-operatively. Post-operative function was assessed by scoring systems - Creighton-Nebraska Health Foundation Assessment Scale (C-N score) and Ankle-Hindfoot Scale AOFAS (A-H score) and radiographic assessment revealed the accuracy of the position. According to our experience we could advocate percutaneous reduction and screw fixation as the method of choice for Sanders type IIC tongue- type fractures and modified Palmer approach with screw alone, C-nail, K-wires or alternatively an open plate osteosynthesis in Sanders type IIAB depression fractures. For Sanders Type III fractures, we find ORIF with a plate as the most suitable method and an external fixation supplemented with K-wires for Sanders Type IV.

Locking Plate Fixation with Multiple Telescoping Sliding Screws for Femoral Neck Fractures.

BACKGROUND: Non-displaced femoral neck fractures are mostly treated with internal fixation, while in dis-placed fractures this surgical option is under debate and the benefits are still not clear. The purpose of this study was to identify the factors that affect the treatment of non-displaced and displaced hip fractures using a head-preserving plate. MATERIAL AND METHODS: From August 2011 to May 2015, we reviewed eighty-two adult patients who had sustained undisplaced and displaced intracapsular femoral neck fracture treated with a locking plate system with telescoping sliding screws. Fracture reduction, healing rate and implant related complications were primary objectives. Other complications (e.g. avascular necrosis, nonunion, hematoma, infection) and revision surgery were recorded as well. RESULTS: According to the Garden classification system, a total of 51.2% fractures were classified as non-displaced (type 1 and 2) and 48.8% were displaced fractures (type 3 and 4). Anatomic reduction was achieved in 58.5% and valgus in 41.5% of patients and it did not influence the healing. Varus reduction was not observed in any case. The total average complication rate was 18.1%, where screw cutout was the most frequent complication (8.5%). The timing of surgery did not affect the healing of femoral neck fractures. Age over 60 years combined with a displaced fracture was associated with impaired healing potential and a higher complication rate. Revision surgery was performed in 17.1% of patients, mainly those with displaced fractures. CONCLUSIONS: 1. The use of a locking plate system with telescoping sliding screws was associated with lower rates of postoperative complications in undisplaced, but also in displaced femoral neck fractures in patients younger 60 years. 2. Patients over 60 years with displaced fractures were more likely to have healing problems and implant failure.

[A Bizarre Parosteal Osteochondromatous Proliferation - Case Report and Review of Similar Hand Lesions Recorded Since 1983].

Bizarre parosteal osteochondromatous proliferation (BPOP) is an unusual lesion mostly affecting the bones of the hand. The mass grows from the bone surface and consists of cartilaginous, osseous and fibrous tissue. The lesion is commonly under/misdiagnosed and confused with other lesions, mostly the osteochondromas. We present a patient with BPOP that initially confused the practitioner and radiologist in their diagnosis. We discuss the clinical, radiologic and histologic characteristics of BPOP of the hand since its first report in 1983 and present its main differential diagnosis. We reviewed 184 cases. Female were affected in 52% and male in 48%. Pro ximal phalanges were most commonly affected, followed by middle phalanges and metacarpals. Pain was reported in 47,9 % of all reported papers. The most common surgical treatment was by excision, and the rate of recurrence was 47.3%.

Antiglide versus lateral plate fixation for Danis-Weber type B malleolar fractures caused by supination-external rotation injury.

PURPOSE: The purpose of this study was to evaluate functional results and the frequency of complications in the distal fibula Danis-Weber type B fractures caused by supination-external rotation injury in a group of lateral and antiglide plate fixation. METHODS: This prospective study evaluated 44 patients with a minimum of one-year follow-up. Patients were divided into two groups: one lateral plate group (24 patients) and group with an antiglide plate (20 patients). The patients of both groups were always positioned supine, and lateral approach was used. In the lateral plate group, the fracture was anatomically reduced, an optional anteroposterior lag screw was placed perpendicular to fracture line, and then the one-third tubular plate was applied on the lateral fibular site. In the antiglide group, the palate was implemented on the posterolateral surface of the fibula and the fracture was anatomically reduced. An optional lag-screw was used. Distal screw fixation was applied deliberately. Functional assessment according to the American Orthopaedic Foot and Ankle Society hind foot-ankle score (AOFAS) were performed at one year after surgery. The complications were recorded. RESULTS: According to Lauge-Hansen classification of supination-external rotation injury, a total of 27 (61.4%) patients was classified as stage 2, 2 (4.5%) patients as stage 3 and 15 (34.1%) patients with stage 4. In the lateral plate group, there were 13 (54.2%) male and 11 (45.8%) female patients. In the antiglide plate group, men comprised 12 (60%) and women 8 (40%) of patients. The AOFAS in the lateral and antiglide group performed one year after surgery was, on average, 93.7 ± 6.1 (range 85-100) and 94.5 ± 6.0 (range 85-100) points respectively. There were no statistically significant differences in both groups (p = 0.37). Complications were observed in 7 (29.3%) patients of lateral plate and 3 (15%) patients of an antiglide plate (p = 0.31). There was no case of tendinopathy. Revision surgery was performed in one patient with superficial infection. CONCLUSION: In the present study, the outcome of the surgically treated Weber type B fractures caused by supination external rotation injury was comparable in both groups. The antiglide plate fixation showed no signs of peroneal tendinopathy, low rate of complications. We believe this technique is safe and a good method of fixation as well as traditional lateral plating.

Carpal Tunnel Syndrome: Symptoms, Causes and Treatment Options. Literature Reviev.

Carpal Tunnel Syndrome (CTS) is the most common form of entrapment neuropathy. Several authors have investigated the anatomical and pathophysiological features of CTS and have identified several parameters that, in combination, play a significant role in its pathophysiology. Advancement in biological research on CTS has enabled the advent of efficient diagnostic techniques such as provocative tests and nerve conduction studies. Sophisticated technologies, such as magnetic resonance imaging (MRI) and ultrasonography (US), have facilitated the diagnosis of CTS. This review article aims at consolidating the relevant medical literature pertaining to the symptoms, pathophysiology, clinical diagnosis and treatment strategies of CTS. It also compares the various methods of diagnosis and discusses their benefits and disadvantages. Finally, it sheds light on the conservative vs. surgical approach to treatment and compares them. While the surgical approach has proved to be more efficient relative to the conservative methods of steroid injections and splinting, many studies have demonstrated both advantages and adverse effects of the surgical methods. Surgical options and complications are discussed in detail. This article comprehensively summarizes all medical aspects of CTS to update medical professionals' knowledge regarding the disease.

iPS cell technologies and their prospect for bone regeneration and disease modeling: A mini review.

Bone disorders are a group of varied acute and chronic traumatic, degenerative, malignant or congenital conditions affecting the musculoskeletal system. They are prevalent in society and, with an ageing population, the incidence and impact on the population's health is growing. Severe persisting pain and limited mobility are the major symptoms of the disorder that impair the quality of life in affected patients. Current therapies only partially treat the disorders, offering management of symptoms, or temporary replacement with inert materials. However, during the last few years, the options for the treatment of bone disorders have greatly expanded, thanks to the advent of regenerative medicine. Skeletal cell-based regeneration medicine offers promising reparative therapies for patients. Mesenchymal stem (stromal) cells from different tissues have been gradually translated into clinical practice; however, there are a number of limitations. The introduction of reprogramming methods and the subsequent production of induced pluripotent stem cells provides a possibility to create human-specific models of bone disorders. Furthermore, human-induced pluripotent stem cell-based autologous transplantation is considered to be future breakthrough in the field of regenerative medicine. The main goal of the present paper is to review recent applications of induced pluripotent stem cells in bone disease modeling and to discuss possible future therapy options. The present article contributes to the dissemination of scientific and pre-clinical results between physicians, mainly orthopedist and thus supports the translation to clinical practice.