Abstract

This study aimed to evaluate the clinical outcomes of paediatric patients who underwent a retrograde drilling treatment for their osteochondritis dissecans (OCD) of the talus. The secondary purpose was to identify factors that are predictive of a failure of the treatment.

A retrospective study was done. All patients treated for talar OCD between 2014 and 2017 were reviewed to extract clinical and demographic information (age, sex, BMI, OCD size and stability, number of drilling, etc). Inclusion criteria were: (1) talar OCD treated with retrograde drilling, (2) less than 18 years, (3) at least one available follow up (4) stable lesion. Exclusion criteria was another type of treatment for a the talar OCD. Additionally, all pre-operative and post-operative medical imaging was reviewed. Outcome was classified based on the last follow-up appointment in two ways, first a score was attributed following the Berndt and Harty treatment outcome grading and second according to the necessity of a second surgery which was the failure group. Chi-square and Mann-Whitney tests were used to compared the success and failure group.

Seventeen patients (16 girls and 1 boy, average age: 14.8±2.1 years) were included in our study group. The mean follow up duration was 11.5 (±12) months. Among this population, 4/17 (24%) had a failure of the treatment because they required a second surgery. The treatment result grading according to Berndt and Harty outcome scale identified good results in 8/17 (47%) patients, fair results in 4/17(24%) patients and poor results in 5/17 (29%) patients. The comparisons for various patient variables taken from the medical charts between patients who had a success of the treatment and those who failed did not find any significant differences.

At a mean follow-up duration of 11.5 months, 76% of patients in this study had a successful outcome after talar OCD retrograde drilling. No statistically significant difference was identified between the success and failure group.

Talar OCD in a paediatric population is uncommon, and this study reviewed the outcome of retrograde drilling with the largest sample size of the literature. Retrograde drilling achieved a successful outcome in 76% of the cases and represents a good option for the treatment of stable talar OCD.

Autologous chondrocyte transplantation has become a possible solution for the treatment of chondral knee lesions. Recently an autologous tissue engineered cartilage (Hyalograft C), using biodegradable scaffolds for cell proliferation, was successfully developed. In osteochondritis dissecans (OCD) the lesion also involves subchondral bone. For this reason we began to use a two-step technique: arthroscopic autologous bone grafting followed by autologouos condrocyte Hyalograft C transplantation after 4–6 months. We treated five patients affected by OCD.

All the patients were clinically evaluated and analysed according to the International Repair Cartilage Society score at 12 and 24 months. The ICRS score showed highly satisfactory clinical results in all treated patients at 12 and 24 months; CT and MRI evaluation had demonstrated a good articular surface reconstruction with complete bone defect restoration at a short 12-month follow-up period. The autologous chondrocyte transplantation provides highly satisfactory clinical results.

This second-generation autologous tissue-engineered cartilage transplantation avoids the use of periosteal flap, simplifies the surgical procedure and permits use of an arthroscopic approach. In association with autologous bone grafting, bone loss can also be restored in order to recreate a perfect articular surface. The preliminary clinical and histological results are encouraging but longer follow-up is required to better evaluate this technique.

Background: Seven cases of osteochondritis dissecans (OCD) of the tarsal navicular bone have been described mainly radiologically.

Aims: We report our experience with additional 6 patients which represent the largest series described, and conclude about the treatment modalities in this unique type of OCD.

Methods: All patients who had OCD of the tarsal navicular bone during the years 1993 and 1998 were evaluated. The parameters which were examined were the age and sex of the patients, the location of pain, duration of symptoms, and any trigger mechanism if this was noted. The various treatments used for these patients as well as their outcome were recorded.

Results: Six patients were treated by us between 1993 and 1998 (follow up 3–7 years). There were 4 males and 2 females aged between 14 and 35 years (mean 21 years). All patients had pain in the dorsal aspect of the midfoot, and painful limitation in midfoot movements. Duration of symptoms varied between 4 months and 1 year. In 3 patients basic training in army service and in one running short distances triggered the pain. In 3 patients an accompanying stress fracture of the navicular bone was developed. Three patients were managed conservatively. Two patients underwent excision, curettage and drilling, and one patient underwent excision and fusion. All patients, whether treated conservatively or surgically, still suffer form pain in activities and painful limitation of midfoot motion.

Conclusions: OCD of tarsal navicular bone affects mainly young patients. Physical efforts are the trigger mechanism for the symptoms. The clinical presentation includes painful limitation in midfoot motion. The outcome is reserved both for conservative or operative treatment.

One of the most important factors influencing therapeutical decisions in orthopaedic surgery are long-term results. Although, osteochondritis dissecans (o.c.d.) of the femoral condyles is the most often occurring location little is known about long-term results. Furthermore, it is of interest to see the time course of such patients regarding the development of secondary osteoarthritis. Thus, it was the aim of our study to re-analyse patients suffering from o.c.d. of the femoral condyle which had been operated have been followed up after a medium time-intervall.

Material & methods: 97 of 147 with o.c.d. of the femoral condyles which were operated using different surgical techniques depending on the stage were followed-up clinically (Lysholm-Score) & radiologically (Arcq- classification/Tapper- & Hoover-score for OA). Results were analysed depending on the age, stage and surgical technique. In 2nd follow-up ten years after the first follow-up patients were reexamined with the same clinical and radiological scores.

Results: At 1st follow-up we found a median Lysholm-Score of 83.7 (21–100, SD 19.6) pts.. Regarding the OA-changes in 56.3% no changes, in 21.9 % 1°-changes, in 3.1% 3°-changes, in 6.3 % 3°-changes & in 12.5 % 4° changes. The mean stage postop. was 0.97 SD 1.4. Ten years later similar results were found: in 56.3% no osteoarthritic changes were seen. 1°-changes were found in 21.9%, 2°-changes in 3.1% and 3°-changes in 6.3% and severe OA 4°-changes were found in 12.5%. In comparison to the 1st follow-up at the 2nd follow-up no individual changes could be detected in 73 %, a slight impairment in 11.5 % & a slight improvement in 15.4%. In most of the patients osteoarthritic changes were slight & did not show a severe impairment after a mean of 20.3 years.

Depending on the age (the stage of the growth plate open vs. closed) adolescents exhibited no or slight oa-changes in 83.3% & moderate changes in 16.7%. Severe oa-changes were not detectable. Adults exhibited a distinct higher incidence of oa (no o.-a.: 37.5%/1°: 25%/2°: 12.5% 3°:/12.5%/4°:12.5%). Regarding the surgical technique retrograde technique leaving the cartilage layer intact resulted in distinct better results than those perforating the cartilage layer.

Conclusion: Best long-term results with a low incidence of OA are to obtain in cases with o.c.d. with intact cartilage layer not necessitating cartilage damage. Worst results are seen in adult patients with 4°-lesions.

Objectives

Surgical treatment is standard for advanced osteochondritis dissecans (OCD) of the humeral capitellum. When cartilage is seen to be separated or completely detached, this fragment fixation is not usually applied. There have been reports of cases in which advanced OCD of the humeral capitellum progressed to osteoarthritis (Fig), particularly in cases which involved the lateral wall. In these cases, every attempt should be made to reconstruct the lateral wall to avoid osteoarthritis. In this study, we followed up cases with rib osteochondral autograft transplantation technique.

Introduction and purpose: Femoral osteochondritis dissecans (OCD) is a process of unpredictable clinical course and uncertain aetiology (vascular, post-traumatic or microtraumatic). Its prognosis is based on diagnostic imaging (MRI and scintillation scanning) and age (Multicentre EPOS OCD Study). In our study we analysed the influence of the alignment of the lower limbs in femoral OCD.

Materials and methods: From 2000–2004 we studied 22 cases in 19 patients with femoral OCD. We carried out a tele-radiographic study of the lower limbs with weight-bearing, recording the location of the OCD according to Cahill, the femorotibial angle (n=87.5° ±2°) and the mechanical axis of the limb, which was considered normal when it went through the two tibial spines (Cahill zone 3).

Results: The mean age was 13.4 years (r: 10–28). The OCD was located in the medial condyle in 16 cases and the lateral in 6. We found changes in the femorotibial angle in 12/22 (55%) and of the mechanical axis in 18/22 (82%). In the cases with worst prognosis and loose bodies (7 cases), 100% showed changes in the mechanical axis.

Conclusions: There is a strong relation between OCD and changes in the lower limb alignment. The most sensitive radiological measurement is the mechanical or weight-bearing axis. This finding confirms the good prognosis of the lesion in children, since they undergo physiological changes in the femorotibial angle and constant changes of the mechanical axis until growth is complete.

Purpose of study: To search and analyse the results of autologous osteochondral transplantation on patients with osteochondritis dissecans of the talus.

Material and method: From 1997 until 2000, 10 patients with 3dr to 4th degree osteochonditis dissecans of the taus were treated with autologous osteochondral transplantation. Their average: age was 33,7 years, and follow up time:32,4 months. Clinical evaluation in accordance with the Finsen classification system as well as radiological evaluation was conducted.

Afterwards arthroscopy with transplantation of autologous osteochondral grafts was performed. An osteomy of the medial malleolus was necessary by 4 patients. Non weight bearing and continuous passive motion for 6 weeks was advised.

Results: The average Finsen score showed improvement: From 3,6 preoperatively to 1 (excellent) postoperatively. Full coverage of the defects was observed at 12 month follow up with MRI in 9 patients and arthoscopically in 3 patients.

Conclusion: This method of treatment presents very good clinical results and sends a hopefull message on the prognosis of the ankle joint in cases of osteochondral damage.

Introduction

Osteochondritis dissecans (OCD) is a localised disorder of subchondral bone and the overlying articular cartilage. The most commonly used classification systems involve arthroscopy and MRI.

Aim

To investigate the correlation between arthroscopic and MR findings in patients with OCD of the talus.

Methods

16 ankles in 14 patients with radiographically proven OCD were reviewed. Nine were male and five female. Mean age was 35yrs (range 18–64yrs). The lesions were staged independently using the Guhl1 arthroscopic and Dipaola2 MR classification systems.

Results

Arthroscopically there were eight stable and eight unstable lesions. Of the eight stable lesions, MRI staged five as stable and three as unstable. Of the eight unstable lesions, MRI staged six as unstable and two as stable. This gives a sensitivity of diagnosing unstable lesions as 0.75, with a specificity of 0.63.

Conclusions

This small study demonstrates that MR scans may have some limitations in classifying OCD lesions of the talus. Possible explanations are discussed. We propose that MRI findings, of OCD of the talus, should not be taken in isolation, but correlated with the patients symptoms and signs to avoid unnecessary arthroscopy.

The outcomes of various operative methods for osteochondritis dissecans of the femoral condyles were reviewed, and choice of these operative methods were discussed.

Twenty-four cases (19 males and 5 females) which underwent operative treatments were reviewed. The operative methods included drilling, repositioning and fixation of the osteochodral fragment, and bone graft or osteochondral graft. The minimum follow-up period was two years. The medial femoral condyle was involved in 17 cases, and the lateral, in seven. Lateral discoid meniscus or meniscal injury was combined in all the 7 cases in the lateral. The operative methods were decided from the condition of the cartilage. Drilling was performed in cases with no or minimal cartilage damages (10 cases). Repositioning (if required) and fixation of the fragment using absorbable pins was carried out in cases with a partial or total fragmentation (7 cases). Bone graft or osteochondral graft was performed when the original site was already degenerated (7 cases). Partial meniscectomy was added when the meniscal injury was combined.

In patients who received drilling, the lesion healed radiographically in all the cases and they complained of no or minimal symptoms. In patients who received the fragment fixation, re-union of the fragment was observed in 71% and the clinical outcomes were satisfactory in most of the cases. In patients who received bone graft or osteochondral graft, although union of the graft was observed in all the cases radiographically, 71% of the patients complained of residual pain.

From the results, drilling is sufficient if the cartilage surface is not damaged. When the fragmentation occurred already, the fragment should be repositioned and fixed to the original site before degenerated, as its clinical symptoms were much better than those with bone graft or osteochondral graft.

The purpose of this study was to describe a clinical evaluation of the etiological factors in osteochondritis dissecans (OCD) of the knee from radiographic and arthroscopic findings.

Twenty-two knees of 20 patients (16 male and 4 female, 16.1 years old in average at surgery) with symptomatic OCD of the femoral condyle were studied.

The medial femoral condyles were affected in 16 knees of 14 patients (medial group) and the lateral femoral condyle in 6 knees of 6 patients (lateral group). These two groups were compared using radiological location and arthroscopic findings. In radiography, the location of OCD was classified in accordance with Cahill et al. (1989). On the anteroposterior view, five zones were numbered 1 to 5 from medial to lateral. On the lateral view, three zones were labeled A,B and C from anterior to posterior.

In the medial group, the locations of OCD were 23BC(12), 2BC(1), 23ABC(1) and 23C(2); 14(88%) of 16 knees involved in non-meniscal area. In the lateral group, the locations of OCD were 45C(4), 5C(1) and 4BC(1); 5(83%) of 6 knees involved in meniscal area. In arthroscopy the medial group did not have medial meniscal tear, while the lateral group had 5 lateral meniscal lesions of 6 knees; 3 discoid meniscus (2 with tear and 1 without tear), 2 bucket-handle type tear and one no meniscal lesion.

Lateral meniscal lesions (with or without discoid) might cause OCD of the lateral femoral condyle. In the medial femoral condyle, we thought that OCD did not relate to meniscal lesions.

Introduction and purpose: An analysis was made of the patients’ clinical and radiographical evolution after surgical treatment of osteochondritis dissecans of the knee (ODK) by means of reinsertion, abscission and an osseocartilaginous autograft. An assessment of prognostic factors was also performed.

Materials and methods: Retrospective revision of 30 patients (mean age: 30 years), 5 of them with bilateral involvement. A reinsertion of the fragment was performed in 11 knees, an abscission was used in 18 and an autograft in 6. A clinical assessment using Hughston’s criteria and SF12 was carried out; a radiographical evaluation was also performed using weight-bearing A/P views with the knee flexed 45°. Using the variance analysis test, a study was made of the relationship between clinical status, age, localization, extension, stability, type of treatment, timescale of evolution and degree of joint impingement. The average evolution was 19 years.

Results: Pain was reported as mild or nonexistent by 75, 50 and 21% of patients treated with reinsertion, abscission and grafting respectively. The higher the degree of joint impingement, the worse the patients’ pain level and their joint balance. At the time of treatment, the highest degrees of joint impingement were found in older patients, in lesions in weight-bearing areas, lesions with an intraarticular free fragment, lesions treated with grafting and those with over 15 years’ evolution.

Conclusions: Osteoarthritic changes are frequent after surgical treatment of osteochondritis dissecans, especially in lesions situated in weight-bearing areas. The more joint impingement there is, the worse the expected clinical prognosis. We recommend early treatment of symptomatic lesions and the reinsertion of the osteochondral fragment.

Aims: This study aimed to assess the outcome of arthroscopic debridement and removal of loose bodies from the elbows of patients with OCD of the capitellum who had previously failed non-operative treatment. Methods: Patients who had been treated arthroscopically for symptomatic OCD of the capitellum after failing non-operative management for 6 months were invited for review. They were assessed clinically, by an independent examiner using a modern elbow outcome score, and radiologically. In addition details of sporting involvement and satisfaction of outcome were ascertained. Results: 29 patients/elbows (91% follow up rate) were assessed at a mean follow up period of 77 months. There were 20 males and 9 females with an average age at operation of 22 years. There were no operative complications. 26 patients had none or mild pain and were able to complete activities of daily living with minimal impairment. 27 patients had been regularly involved in sports (Olympic and professional to recreational levels) only 4 of whom had to give up the sport because of ongoing problems. 5 of 6 elite gymnasts and 10 of 11 rugby players were able to fully resume their sport. 11 patients (38%) had recurrence of locking episodes. There was an average 5û loss of ßexion and a 10û loss of extension while the grip strength remained normal. Radiographs demonstrated that most of the capitella had not remodelled. 28 (97%) patients had a good or excellent outcome. Conclusions: This study has demonstrated that arthroscopic treatment of recalcitrant OCD of the capitellum is a safe procedure resulting in satisþed patients most of whom can return their previous level of sports but there is a risk of recurrent locking symptom.

Purpose: We present the rate of osteochondritis disse-cans in a specific group of patients and the results after treatment which was done arthroscopic.

Material-Method: During a period from 1995 to 2001, in 39 patients with mean age 23.4 years suffering of knee pain, osteochondritis dissecans was diagnosed. The classification of the lesions was based on magnetic resonance and surgically treatment was decided. In 32 pts, a partially detached lesion was found and reattachment with biodegradable pins took place. In five pts the lesion was recently detached and treated similarly with pinning after debridement of the crater. In the last two patients the detachment was old, the osteochondral segment was removed and drilling took place.

Results: All patients were followed up for two years and the evaluation was based on the Lyscholm score. Successful healing certified radiologically was achieved in 33 patients.

Conclusion: Osteochondritis dissecans of the knee is seen between young adults who participate in sports activities. The arthroscopic treatment in our clinic was successful in the 84% of patients with good and excellent clinical results.

Purpose of the study: Conservative surgical treatment of osteochondritis dissecans (OCD) in adults raises the problem of integration of the sequestered bone. Mechanical techniques using screw fixation are often insufficient to achieve healing. Adjunction of a biological fixation with osteochondral graft tissue for a mosaicplasty might favour integration of the fragment. The purpose of this study was to assess the short-term outcomes in an initial series using a technique called fixation plus where screw fixation is associated with mosaiplasty.

Material and methods: This was a retrospective analysis of eight adults who underwent surgery from 2003 to 2008 for stage IIB or III (Bedouelle) OCD of the medial condyle. Loss of subchondral tissue could be filled with a cancellous graft. Clinical and radiographic (Hugston) parameters were noted. At three months, the screws were removed arthroscopically. The ICRS-OCD score was noted. At six months, five patients had an arthroMRI to evaluate fragment integration, determine its signal and vitality.

Results: Mean follow-up was 17.4 months (range 3–36). The Hugston score improved from 1.6 (0–3) preoperatively to 3.4 (2–4) postoperatively and the radiological score from 2.5 (2–4) to 3.2 (3–4). The arthroscopy performed to remove the screws revealed integration of the OCD fragment. The ICRS-OCD score was I in two cases, II in five and III in one. The postoperative arthroMRI confirmed continuity with the cartilage at the periphery of the fragment, with no passage of contrast agent into the defect.

Discussion: Screw fixation of OCD fragments is often followed by nonunion and thus failure. Moasaicplasty is an alternative but does not preserve quality cartilage cover (curvature, thickness, cover). The technique proposed here ensures osseous integration of he fragment, complete cartilage cover, and a smaller number of osteochondral pits. Fixation Plus associates mechanical and biological fixation with good preliminary clinical results. Comparative longer term assessment is needed to confirm its pertinence.

Introduction: A number of surgical techniques have been described for the operative treatment of late stage osteochondritis dissecans (OCD) in the knee and ankle that have failed nonoperative management. However, no particular technique has been universally successful. We report the results of a new technique using retrograde drilling combined with the use of a novel collagen based bone void filler to prevent mechanical failure of the joint surface. The purpose of this study was to evaluate the results of this new technique and analyze the efficacy of both collagen Type-1 based osteoinductive bone void fillers Colloss and Colloss E with and without additional bone grafting.

Methods: The osteoinductive bone void fillers Colloss (bovine) and Colloss E (equine) are bone inducing collagenous sponges. The osteoinductive properties are due to the interactive release of BMP-2, BMP-7, IGF-1 and TGF-beta from the implant and the surrounding host tissue by osteoclastic and osteoblastic action. All surgeries performed in the present series included retrograde drilling procedures for OCD in the talar dome and the femoral condyles. Between 2000 and 2006 eight patients were treated by retrograde drilling or trephine drilling under arthroscopic and fluoroscopic control preventing injury to the cartilage surface. The subchondral cavity was filled with a mixture of 20–40 mg bone void filler and morsellized bone graft. The bone void filler is tamped through the drill guide and into position with a Steinmann pin. Thus, only the subchondral defect was filled but the peripheral area of the drill hole remained empty. Evaluation was achieved by clinical assessment, radiographic, and magnetic resonance imaging examination. The follow-up averaged 24 months up to 48 months.

Results: In all cases, osseous density increased in the Colloss filled subchondral area and mechanical impression of the joint surface could be prevented. Interestingly, clinical examination and follow-up MRI exams demonstrated moderate swelling and joint effusion in 5 of 8 cases for a period of 4 to 10 weeks postoperatively. This may be in part due to the augmentation technique. Nevertheless, good clinical (range of motion, pain) and radiographic results (bony healing) were obtained after this new treatment modality.

Discussion: The subchondral application of Colloss in OCD bone cysts or osteonecrosis induced solid osseous formation at the implantation site. The results of persisting joint reaction such as swelling, pain, and prolonged bone edema in MRI scans may be due to mechanical bearing indicating that augmentation of the defect has to be improved to ensure a solid bony reconstruction. Major advantages of this technique include the ease of performing this procedure, the one-step nature of the procedure, and the ability to avoid violation of stable articular cartilage. In addition, this technique may be repeated according to the size of the lesion.

Although described by Gattelier and Chastang in 1924, the transfibular approach to the ankle has been slow to emerge as a conventional orthopaedic technique. To date, applications have been confined to the treatment of tibiotalar arthrodesis, ankle joint incongruity and exposure of the fractured talus, where the distal fibula is also fractured. While seemingly undocumented, it is also proving effective in mosaic-plasty of the talus. This paper outlines an innovative technique of segmental distal fibula osteotomy and its role in the treatment of osteochondritis dissecans of the postero-lateral talar dome.

The purpose of this study is to describe a surgical procedure for unstable osteochondritis dissecans (OCD) of the capitellum and its results.

Between 1992 and 1997, 11 elbows of 11 patients with OCD of the capitellum were treated in our institution. The average age at surgery was 14.7 years and the ages ranged from 12 to 16 years. All patients were male baseball players affected in the throwing side. The follow-up period was from 31 to 95 months (average: 57 months). All patients underwent internal fixation using the pull out wiring method and bone graft (this procedure was established by Kondo in 1989). All lesions of OCD were not only softening or cracked but also unstable with early separation or partially detached fragment. After surgery, a long arm cast was applied for 3 weeks. After confirming bony union of OCD by X-ray, the wires were removed ranged from 15 to 21 weeks (average 17 weeks) postoperatively. Throwing activity was allowed 6 months after surgery.

At the follow-up, all patients were relieved pain and all except one returned to previous throwing levels. Radiographs showed good healing of OCD and minimum degenerative changes were found in only a few joints.

We concluded that this surgical procedure was an effective treatment for adolescent baseball players with unstable OCD of the capitellum.

To determine if there are osteochondritis dissecans (OCD) lesions of the knee that are so unstable on MRI that they are incapable of healing without operative intervention. A secondary objective was to determine the ability of orthopaedic residents to accurately grade OCD lesions according to the Kijowski criteria of stable and unstable.

A retrospective review was performed of patients who had femoral condyle OCD lesions from 2009-present. Only patients with open growth plates and serial MRIs were included. Each MRI was classified according to the Kijowski classification by a junior orthopaedic surgery resident as well as an MSK trained radiologist. A weighted kappa value was used to assess the inter-rater agreement.

The final analysis included 16 patients (17 knees) with 49 MRI's. The weighted kappa agreement between reviewers for overall lesion stability was moderate (0.570 [95% CI 0.237–0.757]). The initial MRI lesion was graded as stable in 59% (10/17) of the knees. Two of these 10 knees became unstable during the study period, however, both stabilised again on subsequent MRIs, one with surgery and the other without surgery. The initial MRI was graded as unstable in 41% (7/17) of the knees. Two of the seven knees (29%) later demonstrated MRI evidence of lesion stability without surgical intervention.

The most important finding in this study was the ability of unstable OCD lesions on MRI to heal without operative intervention. The ability of an orthopaedic surgery resident to grade these lesions on MRI was moderate.

Familial osteochondritis dissecans (FOCD) is an inherited defect of cartilage and bone characterized by development of large cartilage lesions in multiple joints, short stature and early onset osteoarthritis. We have studied a family from Northern Sweden with FOCD over five generations. All affected family members have a heterozygous missense mutation on exon 17 of the aggrecan gene, resulting in a Val-Met amino acid replacement in the G3 aggrecan C-type lectin domain (CLD). Aggrecan, a major proteoglycan of articular cartilage produced by chondrocytes, has a large protein core richly substituted with sulfated glycosaminoglycan chains. The unique structure, its high concentration within the cartilage extracellular matrix and its ability to form a supermolecular complex with hyaluronan and bind to other matrix proteins all profoundly influence the biomechanical properties of the tissue. Deletion of CLD in a chick aggrecan construct was found to influence its secretion from chondrocytes and human aggrecan constructs carrying the V2303M mutation showed diminished interactions with the ECM proteins tenascin-R, fibulin-1 and fibulin-2. To investigate the pathogenesis of FOCD, we studied chondrogenic differentiation of patient bone marrow mesenchymal stem cells and induced pluripotent stem cells. We demonstrated that the mutation results in accumulation of unfolded or misfolded aggrecan within the lumen of the chondrocyte endoplasmic reticulum. Associated with this is the failure to assemble a normal extracellular matrix. This explains the susceptibility of these patients to cartilage injury and the degenerative changes that lead to early onset osteoarthritis.