Avascular necrosis (AVN), also termed osteonecrosis of the femoral head, is a debilitating condition characterised by cellular death of bone constituents secondary to compromised blood supply. It predominantly affects patients in the third to fifth decades of life and is bilateral in 40–80% of cases, imposing a substantial socioeconomic burden due to loss of productivity in an otherwise young and active population. ^[1]

Corticosteroid use and chronic alcohol consumption together account for the majority of non-traumatic cases in the Indian subcontinent, while idiopathic disease, sickle cell trait, and post-traumatic causes constitute the remainder. Epidemiological series from Indian tertiary care centres have reported a rising incidence of steroid-induced osteonecrosis, attributed in part to widespread and often unsupervised use of corticosteroids for various systemic illnesses. ^[2,3]

The natural history of untreated AVN is unfavourable: more than 80% of hips with symptomatic osteonecrosis progress to femoral head collapse within 1 to 4 years of diagnosis, ultimately necessitating total hip arthroplasty (THA). While THA offers reliable pain relief in older patients, its long-term durability in young, active individuals remains a concern because of the increased likelihood of revision surgery over a patient's lifetime. This has driven sustained interest in joint-preserving procedures capable of arresting or reversing the disease process before irreversible collapse occurs. ^[4]

Core decompression, first described in the 1960s and popularised through the following decades, remains the most widely used joint-preserving procedure for early-stage (pre-collapse) AVN. It is believed to relieve intraosseous hypertension and to stimulate a localised healing response through vascular ingrowth. However, the outcomes of core decompression alone are inconsistent, with reported success rates ranging widely depending on lesion size, stage, and etiology. This variability has prompted numerous attempts at biological augmentation of core decompression, including autologous bone marrow concentrate, demineralised bone matrix, growth factors, vascularised and non-vascularised bone grafting, and, more recently, tissue-engineered constructs employing culture-expanded osteoprogenitor cells. ^[5,6]

Several Indian orthopaedic centres have contributed early clinical experience with biological augmentation of core decompression in osteonecrosis, reporting encouraging short- and medium-term functional outcomes with autologous bone marrow-derived cells, which lent support to the hypothesis that enhancing the local osteogenic and angiogenic milieu at the necrotic focus could favourably alter the natural history of the disease. ^[7,8]

Autologous cultured osteoblasts represent a further refinement of this biological approach. Unlike a single injection of unconcentrated or minimally processed bone marrow aspirate, ex vivo culture expansion allows generation of a substantially larger, more homogeneous population of osteoprogenitor cells committed toward the osteoblastic lineage prior to implantation, theoretically providing a more potent and sustained osteogenic stimulus at the necrotic site while remaining entirely autologous and thus avoiding immune rejection or disease transmission. ^[9]

Despite this theoretical promise, long-term (≥5-year) outcome data on autologous cultured osteoblast therapy for AVN of the femoral head remain sparse in the published literature, particularly from Indian and other South Asian cohorts where the disease burden is disproportionately high. The present study was undertaken to report the clinical and radiological outcomes, at a minimum follow-up of six years, of core decompression combined with autologous cultured osteoblast implantation in patients with ARCO Stage I and II AVN of the femoral head. ^[10]

Study Design and Setting

This was a prospective, single-arm, observational case series conducted in the Department of Orthopaedics of a tertiary care teaching institute, with clinical and radiological follow-up extended to a minimum of six years. Institutional Ethics Committee approval was obtained prior to patient enrolment, and written informed consent was taken from all participants.

 Patient Selection

Consecutive patients presenting with hip pain and radiologically confirmed AVN of the femoral head were screened for eligibility.

 Inclusion criteria:

• Age between 18 and 55 years
• Radiologically confirmed AVN of the femoral head, ARCO Stage I or Stage II (pre-collapse disease)
• Persistent hip pain despite a minimum of 6 weeks of conservative management
• Willingness to comply with the prescribed follow-up protocol

 Exclusion criteria:

• ARCO Stage III or IV disease (established femoral head collapse or secondary osteoarthritis)
• Active local or systemic infection
• Known malignancy or coagulopathy
• Pregnancy
• Inability to attend scheduled follow-up

Fifteen hips in 13 patients (two patients with bilateral disease underwent unilateral cell-augmented core decompression on the more symptomatic side, with the contralateral hip managed separately and excluded from outcome analysis) met the eligibility criteria and were enrolled. Radiological staging was performed using plain radiographs and magnetic resonance imaging (MRI) and classified according to the Association Research Circulation Osseous (ARCO) system.

 Harvest and Culture of Autologous Osteoblasts

Under aseptic precautions, 20–30 mL of bone marrow aspirate was harvested from the ipsilateral posterior superior iliac spine 2–3 weeks prior to the index procedure. Mononuclear cells were isolated by density-gradient centrifugation and seeded in osteogenic culture medium supplemented with dexamethasone, ascorbic acid, and beta-glycerophosphate to promote osteoblastic differentiation. Cells were expanded through 2–3 passages under Good Manufacturing Practice–consistent laboratory conditions, with sterility, viability (>90% by trypan blue exclusion), and osteoblastic phenotype (alkaline phosphatase positivity and alizarin red staining for matrix mineralisation) confirmed prior to release for clinical use. A mean of 8–10 million culture-expanded osteoblasts, suspended in approximately 3–5 mL of autologous plasma-based carrier, was prepared for implantation.

 Surgical Technique

All procedures were performed by the same senior surgical team under spinal or general anaesthesia, with the patient supine on a fracture table and under image intensifier guidance. A single or multiple small-diameter core decompression tract(s) (3.0–4.5 mm) were drilled from the lateral subtrochanteric cortex into the necrotic segment of the femoral head, confirmed on both anteroposterior and lateral fluoroscopic views. The necrotic core was gently curetted where feasible, and the culture-expanded autologous osteoblast suspension was then delivered directly into the decompression tract and necrotic focus using a specially prepared delivery cannula. The wound was closed in layers over a suction drain, which was removed at 24–48 hours.

 Post-operative Protocol

Patients were mobilised with touch-down weight bearing using crutches from the first post-operative day, progressing to partial weight bearing at 4 weeks and full weight bearing by 8–12 weeks, guided by clinical and radiological findings. Standard thromboprophylaxis and analgesia protocols were followed. Patients were reviewed at 6 weeks, 3 months, 6 months, 1 year, and annually thereafter up to a minimum of 6 years.

 Outcome Measures

• Clinical function: Harris Hip Score (HHS), recorded pre-operatively and at each follow-up visit
• Pain: 10-point Visual Analogue Scale (VAS)
• Radiological outcome: serial plain radiographs and MRI at 1, 3, and 6 years, staged according to ARCO classification
• Failure was defined as radiological progression to femoral head collapse with a mechanical axis deviation warranting conversion to THA, or clinical deterioration in HHS to the poor category (<70) necessitating salvage surgery

 Statistical Analysis

Data were analysed using standard statistical software. Continuous variables are expressed as mean ± standard deviation (SD). Pre-operative and serial post-operative HHS and VAS scores were compared using repeated-measures analysis of variance (ANOVA) with post-hoc paired comparisons; a p-value < 0.05 was considered statistically significant. Kaplan–Meier survivorship analysis, with conversion to THA as the endpoint, was used to estimate hip-preservation survival at 6 years.

Fifteen hips in 13 patients (12 men, 3 women) with a mean age of 33.8 ± 8.4 years (range 22–48 years) were included, with a mean follow-up of 6.3 ± 0.4 years (range 6.0–7.1 years). The demographic and clinical profile of the cohort is summarised in Table 1.

Table 1. Demographic and clinical characteristics of the study cohort (n = 15 hips)

Individual case-wise clinical and radiological outcomes are presented in Table 2.

 Table 2. Case-wise clinical and radiological outcomes at final (6-year) follow-up

 Clinical Outcomes

The mean Harris Hip Score improved from 56.5 ± 6.2 pre-operatively to 72.3 ± 5.8 at 6 months, 81.6 ± 5.1 at 1 year, and 86.8 ± 8.5 at final (6-year) follow-up (p < 0.001, repeated-measures ANOVA). The greatest rate of improvement occurred within the first 12 months, with scores plateauing between the 2- and 6-year follow-up intervals. Correspondingly, the mean VAS pain score decreased from 6.5 ± 0.9 pre-operatively to 1.8 ± 1.3 at final follow-up (p < 0.001). Serial mean HHS and VAS scores at each follow-up interval are shown in Table 3.

 Table 3. Serial mean Harris Hip Score and VAS pain score over the 6-year follow-up period

Radiological Outcomes

At final follow-up, 12 of 15 hips (80%) demonstrated no radiological progression beyond their baseline ARCO stage, with evidence of healing and reconstitution of subchondral bone density on MRI. Three hips (20%) — two originally ARCO Stage II and one Stage I — progressed radiologically to Stage III with mild-to-moderate femoral head collapse (<2 mm articular step-off) over the follow-up period. Of these, one hip (6.7% of the total cohort) progressed further with functional deterioration (final HHS 72, VAS 4) and underwent conversion to total hip arthroplasty at 48 months post-index procedure. The remaining two hips with radiological collapse remained clinically well-compensated (HHS 78 and 76) and did not require further surgery at the time of final follow-up. Stage-wise radiological progression is detailed in Table 4.

Table 4. Radiological (ARCO) stage distribution — pre-operative versus 6-year follow-up

Kaplan–Meier survivorship analysis, using conversion to THA as the endpoint, demonstrated a hip-preservation survival rate of 93.3% at 6 years for the cohort as a whole, and 100% for hips presenting in ARCO Stage I versus 88.9% for hips presenting in ARCO Stage II.

 Complications

No intra-operative complications, deep infections, neurovascular injuries, or graft-related adverse events were recorded. Minor, self-limiting complications are summarised in Table 5. No patient required blood transfusion, and there were no donor-site fractures.

 Table 5. Complications recorded during the study period (n = 15 hips)

The management of pre-collapse avascular necrosis of the femoral head continues to challenge orthopaedic surgeons, particularly given the predominantly young age at presentation and the poor long-term durability of arthroplasty in this population. Core decompression alone has produced variable results, with several Indian series reporting satisfactory outcomes in only 60–70% of Stage I and II hips at intermediate-term follow-up, prompting a search for adjunctive biological strategies capable of improving on these figures. ^[11,12]

The rationale for cellular augmentation rests on the observation that osteonecrotic bone is relatively deficient in osteoprogenitor cells at the necrotic-viable bone interface, and that supplementing this deficient population may accelerate creeping substitution and bone remodelling before mechanical failure of the subchondral plate occurs. Early Indian experience with autologous bone marrow injection into core decompression tracts reported functional improvement in a majority of Ficat Stage I and II hips at 2- to 3-year follow-up, findings that were broadly consistent with contemporaneous international series and provided the impetus for subsequent refinement using culture-expanded, lineage-committed osteoblasts rather than unprocessed marrow aspirate. ^[13,14]

The present series demonstrates that core decompression combined with autologous cultured osteoblast implantation produced statistically and clinically meaningful improvement in both pain and function, sustained to a minimum of six years, with a hip-preservation rate of 93.3%. These outcomes compare favourably with historical series of core decompression alone, and are broadly concordant with medium-term results reported from other Indian centres using bone marrow-derived cellular augmentation, lending indirect support to the hypothesis that a more concentrated, lineage-committed osteoblast population may confer additional benefit over unprocessed marrow injection, although a direct head-to-head comparison was beyond the scope of this study. ^[15]

The stage-dependent difference in outcome observed in the present cohort — 100% preservation in Stage I versus 88.9% in Stage II hips — is consistent with the broader literature on joint-preserving surgery for osteonecrosis, which consistently identifies pre-operative stage and lesion size as the dominant predictors of outcome, regardless of the specific biological adjunct employed. This underscores the importance of early diagnosis and intervention before the onset of even subtle radiological collapse, since the biological potential for healing appears to diminish substantially once mechanical failure of the subchondral bone has begun.

The three hips that progressed radiologically in this series shared etiological features (alcohol-associated and post-traumatic disease) and comparatively larger necrotic segments on baseline MRI, suggesting that etiology and lesion volume may modulate the response to cellular therapy independent of ARCO stage at presentation. This observation, while limited by the small sample size, is consistent with reports that steroid- and alcohol-associated osteonecrosis, particularly with combined anterolateral and central lesion patterns, may respond less favourably to joint-preserving interventions than idiopathic or post-traumatic disease of comparable stage.

Several limitations merit consideration. First, this was a single-arm case series without a concurrent comparison group undergoing core decompression alone or augmentation with unprocessed bone marrow concentrate; the observed improvement, while substantial, cannot be definitively attributed to the cultured osteoblast component in isolation. Second, the sample size of 15 hips, while providing a meaningful minimum 6-year follow-up rarely reported for this technique, limits the precision of subgroup and survivorship estimates. Third, the cost, laboratory infrastructure, and regulatory requirements associated with ex vivo cell culture may limit widespread applicability of this technique outside specialised centres. Finally, functional and radiological assessment, although protocol-driven, was not entirely blinded, which introduces a potential source of observer bias.

Notwithstanding these limitations, the sustained improvement in Harris Hip Score, marked reduction in pain, and high rate of hip preservation observed over six years support the continued investigation of autologous cultured osteoblast augmentation as a viable joint-preserving strategy in early-stage AVN of the femoral head, particularly in resource settings such as India where the burden of steroid- and alcohol-associated osteonecrosis in young adults remains high. Adequately powered randomised controlled trials comparing this technique against core decompression alone and against other biological adjuncts are needed to define its precise role in the treatment algorithm.

In this series of 15 hips with ARCO Stage I and II avascular necrosis of the femoral head followed for a minimum of six years, core decompression combined with implantation of autologous cultured osteoblasts resulted in significant, durable improvement in hip function and pain, with radiological healing or stable disease in 80% of hips and a hip-preservation rate of 93.3% at final follow-up. The technique was safe, with no major procedure-related complications. These findings support autologous cultured osteoblast augmentation as a promising biological hip-preservation strategy for early-stage osteonecrosis, while highlighting the need for larger, controlled, multicentric studies with long-term follow-up to establish its definitive role relative to other joint-preserving techniques.

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