Introduction

Knee pain affects approximately 25% of adults and is a common reason for seeking medical care in the general population, accounting for nearly 4 million primary care visits each year.1 In these patients, a common imaging finding is bone edema, which can be attributed to multiple causes, such as bone contusion, infections, rheumatic diseases, or tumors.2,3 However, there is another group of patients, generally between the ages of fifty and sixty, in whom knee pain and the finding of bone edema could be attributed to the presence of osteonecrosis (ON) of the knee or to primary bone edema.2,4

ON can occur in various anatomical locations, with the knee being the second most affected site after the hip.5,6 Knee ON is a progressive disease of the subarticular bone that can eventually lead to subchondral collapse and severe osteoarthritis.5–8 It was first described in 1968 by Ahlback et al. as the spontaneous onset of a lesion that typically affected the medial femoral condyle;5–7,9,10 however, subsequent studies identified patients with characteristics and symptoms that did not fully align with the initial descriptions, leading to its current classification into three distinct conditions: Spontaneous Osteonecrosis of the knee (SONK), secondary ON, and post-arthroscopic ON.5-7,10

SONK is the most common form5,7 and, unlike secondary ON, its exact etiology is unknown due to its complex and multifactorial nature,6–8 although two main theories have been proposed (an underlying traumatic event or vascular involvement).10–13 It occurs predominantly in individuals aged ≥50 years, being more common in women (3:1 ratio) and in older adults (incidence of 3.4% and 9.4% in people aged ≥50 years and ≥65 years, respectively).5–8,13–15

Regarding its clinical presentation, SONK is typically unilateral (>95% of cases) and affects a single condyle, primarily the Medial Femoral Condyle (MFC).6–8,11–13,15 The most common symptom is acute-onset, non-traumatic, and disabling knee pain. Generally, the pain is localized on the affected side of the knee, and patients report that it worsens at night and with weight-bearing activities.5,7,8,10,12,14 Furthermore, the most common finding on physical examination is focal tenderness along the joint line, particularly over the MFC,5,6,9,14,16 but the presence of mild effusion and reduced range of motion due to pain are also common.7,8 When it comes to diagnosis, bone edema and focal subchondral lesions are cardinal signs,7,8,10,11 which is why in patients with acute unilateral knee pain of unclear etiology and imaging findings of bone edema, clinical suspicion of SONK should be high.

Although the initial evaluation of patients with these clinical features includes knee X-rays (anteroposterior, lateral, and oblique views),5,7 these are generally normal in the early stages of the disease, especially if not much time has elapsed since the onset of symptoms; therefore, the diagnosis is often missed in the early stages if more sensitive imaging techniques are not used.5,7,8,10,12 According to the literature, magnetic resonance imaging (MRI) is the gold standard for diagnosing SONK in its early stages due, on the one hand, to its high sensitivity and specificity for detecting and evaluating bone edema, a cardinal sign of the disease present from its onset, and associated lesions;5-8,16-19 on the other hand, to its usefulness in assessing the extent of the disease, including meniscal and chondral damage,6,8,15 which is essential for designing the treatment plan.8 Nevertheless, X-rays can aid in diagnosis in advanced stages, with the presence of radiolucency, sclerosis, and/or subchondral collapse and flattening of the affected condyle being typical findings.5,7,8 In addition, laboratory tests should also be performed to rule out other causes of knee pain, such as infection or inflammatory arthritis.8

Staging and monitoring of disease progression are performed using X-rays.6,7,14 There are two staging systems: the Koshino classification (stages 1–4), based on clinical and radiographic findings, and the Ficat classification (stages I–IV), based on chondral collapse and joint space narrowing evident on X-rays.5–7,13 Treatment for SONK can be conservative or surgical, and the choice depends primarily on the size of the area of ON and the stage of the disease. Generally, conservative management is the first-line treatment for patients with osteonecrotic lesions <3.5 cm² and in early stages. In contrast, lesions >3.5 cm² require surgical management. Lesions between 3.5 cm² and 5 cm² show a high degree of radiographic progression, and those >5 cm² cause condylar collapse.5–8,12,13,20

Conservative treatment includes measures such as protected weight-bearing, oral analgesics, nonsteroidal anti-inflammatory drugs, physical therapy, and the use of wedge insoles,5,7,8,12-20 with satisfactory results in terms of symptom improvement and knee function in most patients if initiated in the early stages.7,12 The use of bisphosphonates has also been proposed as a treatment alternative, as several authors have reported their potential efficacy in halting the progression of osteonecrosis; however, results are inconsistent across studies.5,7,8,12 Another conservative management modality currently under study is pulsed electromagnetic field therapy, which has shown promising results in case series in terms of reducing pain, the size of the necrotic lesion, and the area of bone edema.7,21 Regardless of the treatment protocol, if there is no improvement3–6 months after the start of conservative management, surgical intervention should be considered.7,8

Despite this, there are few studies reporting data on the clinical outcomes achieved with the various conservative treatment regimens used in these patients.22 Given this, the objective of the present study was to present the clinical outcomes achieved in patients with Ficat stage I and II SONK treated conservatively at a healthcare facility in southwestern Colombia, following an institutional management protocol.

Methodology

Type of Study

Descriptive retrospective study.

Study Population Sample

The study population consisted of adults (>18 years) diagnosed with SONK who were treated conservatively at a tertiary care facility in Cali (Colombia) between January 1, 2012, and December 31, 2022. Patients with Ficat stage I or II SONK who were treated conservatively in the clinic’s knee surgery department and for whom knee X-ray and MRI images were available in the institution’s radiology system were included. Patients with an indication for surgical treatment (Ficat III or II), a follow-up period <12 weeks, or incomplete medical record data for the variables of interest were excluded.

It should be noted that all patients presented with the classic symptoms and signs of SONK (acute, non-traumatic unilateral knee pain of moderate to severe intensity, with or without swelling; limping or difficulty walking; bone edema on MRI (Figure 1) that could not be explained by neoplastic, infectious, or degenerative pathology, and associated imaging findings such as subchondral lesions, crescent sign, or low signal in the subchondral band, joint effusion, irregular joint margins, meniscal lesions [meniscal root, meniscal extrusion], or soft tissue edema).

The diagnosis was made after ruling out a history of rheumatic disease, gout, grade III or higher osteoarthritis, sickle cell disease, knee infection, joint effusion within the past year, knee trauma within the past 3 months, knee surgery, alcoholism, smoking, or prolonged use of corticosteroids. In addition, the lead author was responsible for the follow-up of all patients.

Procedures and Variables

Based on a review of the medical records, the following information was collected for each patient: Age; sex; laterality of the affected knee; BMI; FICAT stage at the time of diagnosis; follow-up duration; gait disturbance; history of diabetes; and presence of (self-reported during the initial physical examination) pain; functional limitation in activities of daily living; feeling like the knee buckled; and feel a block to knee motion. In addition, knee X-rays and MRIs were reviewed to obtain information on the following variables: Presence of angular deformity; structure of the knee affected by ON; associated MRI findings; and Ficat stage at the end of follow-up. Treatment effectiveness was determined based on radiographic progression (modified Ficat classification for the knee - Figure 1) and the presence of pain at the end of follow-up.

A. Stage I: No radiographic evidence of osteonecrosis of the knee. The femoral condyles appear normal, with no sclerosis and normal curvature.

B. Stage II: Signs of mottled sclerosis are evident, but the structure of the articular bone remains intact.

C. Stage III: presence of the crescent sign, which is indicative of a subchondral fracture.

D. Stage IV: collapse of the subchondral bone.

Figure 1. Modified Ficat and Arley Classification for the Knee23

Source: Adapted from Calvo et al.24

Description of the Conservative Treatment Initiated

According to the management protocol for patients with suspected SONK established at our institution, once the diagnosis is confirmed, those with early-stage SONK (modified Ficat I and II for the knee - Figure 1) and with symptoms that began less than 3 months should be treated conservatively. The conservative management protocol consists of analgesia with acetaminophen plus codeine or hydrocodone during the first 72 hours after diagnosis, weight-bearing protection (primary measure), use of Acetylsalicylic Acid (ASA) at antiplatelet doses, and vitamin D supplementation therapy (7,000 IU/week), vitamin C (1.5 g/day), and zinc (25 mg/day) until resolution of symptoms and confirmation of remission of the osteonecrotic lesion. Given that available studies show controversial or no clinical benefit for bisphosphonates25-27 and limited evidence for shockwave therapy,2,28,29 these strategies are not used in our protocol. NSAIDs are also not used because they have been shown to delay bone healing.30,31

Once treatment has begun, monthly clinical and radiographic follow-up is performed to assess disease progression and symptoms and to determine whether the response has been adequate or whether surgical management is required. In addition, monthly follow-up should be conducted for at least 3 months and until symptoms resolve and there is radiographic confirmation of lesion remission, or a decision is made to change the therapeutic approach. The management protocol is presented in Figure 2.

Figure 2. Flowchart of the Protocol for Managing Patients with Suspected Knee Osteonecrosis Implemented at the Healthcare Facility where the Study was Conducted

Source: Own elaboration.

Statistical Analysis

The data were entered and organized in a pre-designed template created by the authors in Microsoft Excel and then exported to Stata (version 17; StataCorp, TX, USA) for analysis. Data are described using absolute frequencies and percentages for qualitative variables, and means, medians, standard deviations, and interquartile ranges for quantitative variables, based on the results of the normality test (Shapiro-Wilk). Radiological progression (Ficat classification) between the start of treatment and the end of follow-up was assessed using the nonparametric McNemar test. A level of statistical significance of p<0.05 was considered.

Ethical Considerations

This study adhered to the ethical principles for conducting biomedical research on human subjects established in the Declaration of Helsinki32 and the scientific, technical, and administrative standards for health research set forth in Resolution 8430 of 1993 issued by the Colombian Ministry of Health and Social Protection.33 It was also approved by the Research Ethics Committee of Clínica Imbanaco S.A.S., as per minutes CEI-783 dated June 14, 2023.

Results

A total of 29 patients with SONK were treated at the hospital between January 1, 2012, and December 31, 2022. Of these, 2 were excluded because they underwent surgical treatment (Ficat III), and 2 because their follow-up period was less than 3 months; consequently, 24 patients were ultimately included in the study.

The average age at diagnosis was 69.7±7.4 years; 58.3% were women; in 66.6% of cases, SONK was classified as Ficat stage I; and in 54.2% of cases, the condition affected the left knee. The average BMI was 28.4±4.1 kg/m², 79.1% were overweight or obese, and 12.5% had diabetes mellitus. Regarding the initial assessment, 100% of patients reported moderate to severe pain, 87.5% reported functional limitations in activities of daily living, and gait disturbance and angular deformity were observed in 66.7% and 52.3%, respectively. Regarding MRI findings, the meniscus was the most affected site (62.5%), and meniscal lesions, meniscal tears, and joint effusion were the most frequent associated findings (87.5% of cases each). The demographic, clinical, and imaging characteristics of the patients are presented in Table 1.

Table 1. Demographic, clinical, and imaging characteristics of patients with Ficat I and II SONK treated conservatively (n=24)

Variable	n (%)
Age (years), mean±SD	69.7±7.4
Sex
Female Male	10 (58.3) 14 (41.7)
Laterality
Right Left	11 (45.8) 13 (54.2)
IMC (kg/m²), mean±SD	28.4±4.1
Nutritional Status
Normal weight Overweight Obesity	5 (20.9) 11 (45.8) 8 (33.3)
Diabetes mellitus	3 (12.5)
Functional limitation	21 (87.5)
Feeling of blockage	3 (12.5)
Sensation of giving way	4 (4.2)
Gait disturbance	16 (66.7)
Angular deformity
No Genu varo Genu valgo	10 (41.7) 12 (50.0) 2 (8.3)
Ficat classification at diagnosis
Degree 1 Degree 2	16 (66.6) 8 (33.3)
Structure affected on MRI
Medial condyle Lateral condyle Medial plate Condyle and medial plate	15 (62.5) 2 (8.3) 6 (25.0) 1 (4.2)
MRI finding
Joint effusion Meniscal root tear Meniscal injury Meniscal extrusion Depression or irregularity Subchondral lesion	21 (87.5) 3 (12.5) 21 (87.5) 13 (54.2) 2 (8.3) 17 (70.8)

Source: Own elaboration

SD: Standard deviation; BMI: Body mass index; MRI: Magnetic resonance imaging.

The median follow-up was 4 months (IQR: 3–12 months). At the end of follow-up, disease progression was observed in only 4 patients (16.7%; FICAT I to FICAT II), for a total of 12 patients (50%) with FICAT I and 12 with FICAT II (Figure 3), with no significant differences in radiological progression between the time of diagnosis and the end of follow-up (p=0.125). In addition, the 20 patients who showed no signs of progression (83.3%) reported feeling no pain.

Figure 3. Distribution of SONK according to FICAT classification at the start of treatment and at the end of follow-up

Source: Own elaboration.

Discussion

The findings of this study demonstrate that the conservative management protocol implemented at our institution is effective for the treatment of early-stage SONK, as radiological progression was observed in only 16.7% of patients during follow-up (from Ficat I to Ficat II in all cases); consequently, the treatment approach was not modified for any patient. Furthermore, based on clinical and radiographic findings, surgical management was not indicated in any of the patients at the end of follow-up; that is, conservative management was 100% effective. These results are consistent with those reported in the case series by Jordan et al.12 (96% effectiveness in 40 cases without information on disease classification), and Yates et al.19 (100% in 20 cases of stage I SONK in 14 patients). Other authors have reported lower effectiveness rates of 81.82%34 and 75%.35 Table 2 presents the main characteristics of studies on the effectiveness of conservative management protocols for SONK.

Table 2. Studies reporting data on the use of a conservative management protocol for SONK like the one implemented

Author	Country	Period of Study	Number of Patients	Koshino Classification at the Start of the Study (number of patients by stage 1/2/3/4)	Pre-collapse / Post-collapse Grouping (Koshino ↔ modified Ficat for the knee)*	Duration of Treatment	Conservative Management Protocol Used	Results
Aglieti et al.34, 1983	Italy	1966-1980	105 knees (91 patients), of which 22 were treated conservatively.	0/6/7/6/3-	59% pre-collapse and 41% post-collapse.	The duration of treatment is not reported, but the average follow-up period (3.7 years) was reported.	Weight-bearing exercises, pain relief, and isometric exercises to strengthen the quadriceps.	Satisfactory clinical outcomes were observed in 18 of the knees (81.82%: excellent in 9 and good in 9) at follow-up. Significant differences were observed in knee function before and after treatment (70 points vs. 82 points; p<0.05). During follow-up, the osteonecrotic lesion had almost completely disappeared in one knee (4.54%), had improved in 8 (36.36%), remained unchanged in 7 (31.82%), and worsened in 6 (27.27%)
Marti et al.,35 2000	Switzerland	1992 - 1995	10 patients with medial compartment SONK, 4 of whom were treated conservatively (3 men, 1 woman; average age 59 years).	2/1/0/1	75% pre-collapse and 25% post-collapse.	3 months.	Pain relievers and partial weight-bearing.	Two patients showed clinical improvement after treatment; however, there were no significant differences in the mean Knee Society Score. Regarding radiological evaluation, progression of the lesion was observed in one patient (stage II to IV; 25%). Regarding MRI findings, edema decreased in 3 patients (75%), but the area of necrosis decreased in only 1 (25%).
Yates et al.,19 2007	England	2001 - 2003	20 knees (14 patients: average age: 52 years; 11 men; 3 women).	20/0/0/0	100% pre-collapse.	Patients were treated until their pain subsided. The average time from symptom onset to resolution was 4.8 months.	Weight-bearing restrictions or limitations on activities requiring full weight-bearing, along with pain relief using NSAIDs or acetaminophen.	All patients reported an improvement in their symptoms. In all cases with follow-up MRI (n=19), complete resolution of the abnormal MRI findings was observed, with an average time to resolution of 8 months.
Jordan et al.,12 2015	United Kingdom	2001 - 2014	40 knees (37 patients: average age 55.3 years, 67.5% men).	Classification information not available.	No classification information is available, but it is inferred that 100% occurred prior to the collapse.	6 weeks Average follow-up period: 10 months.	Touch-down weight-bearing exercises under the supervision of the physical therapy department.	All 28 patients for whom scores on functional scales (Tegner, WOMAC, Lysholm, IKDC, EVA) were recorded at the time of symptom onset and at the final follow-up showed statistically significant improvements (p<0.0001).
Akamatsu et al.,14 2017	Japan	2009 - 2013	54 (27 underwent surgical treatment and 27 received conservative management; median age of 74 and 68 years in the conservative and surgical groups, respectively).	10/15/2/0	92.6% before the collapse and 7.4% after the collapse.	It does not specify; they only mention that the follow-up period was 12 months after the onset of symptoms.	Restricted weight bearing and daily activities and nonsteroidal anti-inflammatory medications	No information is provided on radiological progression; the study focuses on predictive factors during the initial assessment of a poor 1-year prognosis from symptom onset (AFT >180 and depth ≥20 mm on MRI). It describes only the initial assessment and does not provide information on radiological follow-up or patient progression.
Fujita et al.,36 2016	Japan	Not specified.	1 (72-year-old man)	0/0/1/0	100% post-collapse.	Approximately 4 months, although it is not specified directly, it is reported that, given the persistence of symptoms and evidence of disease progression on MRI 4 months after the initial evaluation, the patient underwent unicompartmental knee arthroplasty.	Initial nonsurgical treatment included restricted weight bearing on the affected lower leg, hyaluronic acid injections, and administration of NSAIDs	Persistent symptoms with evidence of progression (RNM).

*To facilitate comparison with previous series that used the Koshino classification, we grouped the lesions into pre-collapse (Koshino I–II / Ficat I–II) and post-collapse (Koshino III–IV / Ficat III-IV), since both classifications consistently distinguish between early stages without subchondral collapse and advanced stages with collapse and osteoarthritic changes.5,7,37

The article by Aglieti et al.34 mentions a modified Koshino classification, in which they refer to a Stage V; however, the key distinction lies in the fact that, in this modified classification, the lesions grouped as pre-collapse stages are Koshino I, II, and III (with stages II and III being a subdivision of the former stage II, considering stage II to involve flattening upon weight-bearing, and stage III to involve chondral shadowing associated with clear pre-collapse sequelae), and the post-collapse stages remain Koshino IV and V without changes.

+The treatment performed in the included studies must be consistent with the institutional protocol we are describing: It is a conservative treatment based on restricted weight-bearing (RWB).

NSAIDs: Nonsteroidal anti-inflammatory drugs; MRI: Magnetic resonance imaging.

In the present study, the mean age was 69.7 years, which is higher than the mean ages reported in the studies by Yates et al.,19 Jordan et al.12 and Martin et al.35 (52, 55.3, and 59 years, respectively), but lower than the median age reported by Akamatsu et al.14 for patients who received conservative treatment (74 years) and the age of the patient described in the case report by Fujita et al.36 (72 years).

In this regard, given that most studies reporting conservative management protocols for SONK involve older adults, it could be hypothesized that joint stress in this population - which is much lower than in younger patients - may play a protective role against disease progression, particularly considering that weight-bearing protection, a cornerstone of conservative treatment, might be more effective in this population. Nevertheless, it should also be noted that SONK generally affects individuals aged ≥50 years, being more common in those aged 65 years,5-8,13-15 and that low bone mineral density, a characteristic of the elderly population due to the progressive loss of bone mineral density after the sixth decade of life,39, is a factor associated with the presence of SONK.8,39

The most affected anatomical structure was the medial condyle (62.5%) (Figure 4), followed by the medial meniscus (25%), which is like the findings reported by Jordan et al.12 and Veloz-Serrano et al.7

Figure 4. Magnetic resonance imaging of the right knee (coronal view). Bone edema is observed in the medial condyle, along with irregularity of the joint contour, a subchondral cyst, meniscal extrusion, and edema of the surrounding soft tissues

Source: Image obtained during the study.

In a study involving 54 patients with SONK who underwent either conservative treatment (n=27) or surgical treatment (n=27), Akamatsu et al.,16 found that a femorotibial angle >180° and a chondral lesion depth >20 mm on the sagittal slice of the initial MRI (within the first week following the initial evaluation) were significantly associated with a higher risk of disease progression 1 year after symptom onset. Although it was not possible in our study to evaluate the association between progression to surgical management and angular deformity because femorotibial angle measurements were not available for all patients, a notable finding is that in no patient did SONK progress to a stage requiring surgical treatment.

Another finding worth noting is the high frequency of meniscal tears as an associated injury on MRI (87.5%), which is even more common than the presence of subchondral lesions (70.8%), a typical feature in the natural history of ON. In this regard, Chambers et al.40, in a study that included 12 knees with SONK (11 patients), reported that 11 knees (91.67%) had a medial meniscal tear. Similarly, Nelson et al.41 reported that of 34 knees with SONK (32 patients), 31 (91.18%) had a meniscal tear.

The literature has reported that meniscal extrusion is common in patients with SONK (63–100%);42,43 however, in our study, the proportion of knees with meniscal extrusion was lower (54.2%). Finally, only 12.5% of patients had a meniscal root tear, a much lower proportion than the 62.2% described by Yamagami et al.44 in 45 patients with SONK.

This study has several limitations that should be considered when interpreting the results reported here. First, the small sample size. Second, its retrospective nature implies a potential bias in the data, as it is not possible to guarantee the accuracy of the data recorded in the medical records, especially considering that the analysis period spanned 10 years. Third, the absence of a control group (surgical management) prevents a comparison of the conservative treatment protocol regarding its efficacy in terms of SONK progression. Fourth, the short follow-up period (median of 4 months) makes it impossible to determine whether the concomitant presence of extrusion and meniscal tears is an incidental finding occurring simultaneously with ON or whether it is a predisposing factor. In this regard, prospective studies with longer follow-up periods, larger sample sizes, and the inclusion of control groups (surgical management) are required, as this will allow for a more rigorous evaluation of the effectiveness of conservative management protocols for SONK, such as the one used at our institution.

Conclusion

The conservative management protocol used at our institution yields satisfactory results, as evidenced by the disease progression rate, and none of the patients required surgical intervention at the end of follow-up.

Conflicts of Interest

None declared by the authors.

Funding

None declared by the authors.

Acknowledgments

None declared by the authors.

References

1.Bunt CW, Jonas CE, Chang JG. Knee pain in adults and adolescents: The initial evaluation. Am Fam Physician. 2018;98(9):576-85. PMID: 30325638.

2.Villari E, Digennaro V, Panciera A, Ferri R, Benvenuti L, Cesare F. Bone marrow edema of the knee: a narrative review. Arch Orthop Trauma Surg. 2024;144(5):2305-16. 2024;144(8):3897. https://doi.org/10.1007/s00402-024-05387-2 PMID: 38642163; PMCID: PMC11093815.

3.Tarantino U, Greggi C, Cariati I, Caldora P, Capanna R, Capone A, et al. Bone Marrow Edema: Overview of Etiology and Treatment Strategies. J Bone Joint Surg Am. 2022;104(2):189-200. https://doi.org/10.2106/JBJS.21.00300 PMID: 34780382.

4.Di Già M, Boncinelli D, Losco M, Giron F. Pathophysiology and treatment of bone edema: focus on the knee. International Journal of Bone Fragility. Int J Bone Frag. 2023;3(3):105-11 https://doi.org/10.57582/IJBF.230303.105

5.Karim AR, Cherian JJ, Jauregui JJ, Pierce T, Mont MA. Osteonecrosis of the knee: review. Ann Transl Med. 2015;3(1):6. https://doi.org/10.3978/j.issn.2305-5839.2014.11.13 PMID: 25705638; PMCID: PMC4293480.

6.Mont MA, Marker DR, Zywiel MG, Carrino JA. Osteonecrosis of the knee and related conditions. J Am Acad Orthop Surg. 2011;19(8):482-94. https://doi.org/10.5435/00124635-201108000-00004 PMID: 21807916.

7.Serrano DV, Saseendar S, Shanmugasundaram S, Bidwai R, Gómez D, D’Ambrosi R. Spontaneous Osteonecrosis of the Knee: State of the Art. J Clin Med. 2022; 11(23):6943. https://doi.org/10.3390/jcm11236943 PMID: 36498517; PMCID: PMC9737125.

8.Li D, Shamrock AG, Young JR, Rosenbaum AJ. Spontaneous Osteonecrosis of the Knee. 2024. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–. PMID: 31613502.

9.Ahlbäck S, Bauer GC, Bohne WH. Spontaneous osteonecrosis of the knee. Arthritis Rheum. 1968;11(6):705-33. https://doi.org/10.1002/art.1780110602 PMID: 5700639.

10.Juréus J, Lindstrand A, Geijer M, Robertsson O, Tägil M. The natural course of spontaneous osteonecrosis of the knee (SPONK): a 1- to 27-year follow-up of 40 patients: A 1- to 27-year follow-up of 40 patients. Acta Orthop. 2013;84(4):410-4. https://doi.org/10.3109/17453674.2013.810521 PMID: 23799344; PMCID: PMC3768043.

11.Karantanas AH, Drakonaki E, Karachalios T, Korompilias AV, Malizos K. Acute non-traumatic marrow edema syndrome in the knee: MRI findings at presentation, correlation with spinal DEXA and outcome. Eur J Radiol. 2008;67(1):22-33. https://doi.org/10.1016/j.ejrad.2008.01.053 PMID: 18342472.

12.Jordan RW, Aparajit P, Docker C, Udeshi U, El-Shazly M. The importance of early diagnosis in spontaneous osteonecrosis of the knee - A case series with six year follow-up. Knee. 2016;23(4):702-7. https://doi.org/10.1016/j.knee.2016.04.005 PMID: 27198760.

13.Bhatnagar N, Sharma S, Gautam VK, Kumar A, Tiwari A. Characteristics, management, and outcomes of spontaneous osteonecrosis of the knee in Indian population. Int Orthop. 2018;42(7):1499-508. https://doi.org/10.1007/s00264-018-3878-y PMID: 29552689.

14.Akamatsu Y, Kobayashi H, Kusayama Y, Aratake M, Kumagai K, Saito T. Predictive factors for the progression of spontaneous osteonecrosis of the knee. Knee Surg Sports Traumatol Arthrosc. 2017;25(2):477-84. https://doi.org/10.1007/s00167-015-3839-6 PMID: 26572631.

15.Breer S, Oheim R, Krause M, Marshall RP, Amling M, Barvencik F. Spontaneous osteonecrosis of the knee (SONK). Knee Surg Sports Traumatol Arthrosc. 2013;21(2):340-5. https://doi.org/10.1007/s00167-012-2017-3 PMID: 22534975.

16.Gil HC, Levine SM, Zoga AC. MRI findings in the subchondral bone marrow: a discussion of conditions including transient osteoporosis, transient bone marrow edema syndrome, SONK, and shifting bone marrow edema of the knee. Semin Musculoskelet Radiol. 2006;10(3):177-86. https://dpi.org/10.1055/s-2006-957171 PMID: 17195126.

17.Matcuk GR Jr, Mahanty SR, Skalski MR, Patel DB, White EA, Gottsegen CJ. Stress fractures: pathophysiology, clinical presentation, imaging features, and treatment options. Emerg Radiol. 2016;23(4):365-75. https://doi.org/10.1007/s10140-016-1390-5 PMID: 27002328.

18.Horikawa A, Miyakoshi N, Shimada Y, Kodama H. Spontaneous Osteonecrosis of the Knee: A Retrospective Analysis by Using MRI and DEXA. Open Orthop J. 2016;10(1):532-8. https://doi.org/10.2174/1874325001610010532 PMID: 27990190; PMCID: PMC5120381.

19.Yates PJ, Calder JD, Stranks GJ, Conn KS, Peppercorn D, Thomas NP. Early MRI diagnosis and non-surgical management of spontaneous osteonecrosis of the knee. Knee. 2007;14(2):112-6. https://doi.org/10.1016/j.knee.2006.10.012 PMID: 17161606.

20.Sibilska A, Góralczyk A, Hermanowicz K, Malinowski K. Spontaneous osteonecrosis of the knee: what do we know so far? A literature review. Int Orthop. 2020;44(6):1063-9. https://doi.org/10.1007/s00264-020-04536-7 PMID: 32249354.

21.Marcheggiani Muccioli GM, Grassi A, Setti S, Filardo G, Zambelli L, Bonanzinga T, et al. Conservative treatment of spontaneous osteonecrosis of the knee in the early stage: pulsed electromagnetic fields therapy. Eur J Radiol. 2013;82(3):530-7. https://doi.org/10.1016/j.ejrad.2012.11.011 PMID: 23219192.

22.Lair J, Fink C, Csapo R. Spontaneous osteonecrosis of the knee: A systematic review of conservative treatment approaches [Internet]. Research Square. Research Square; 2021 [cited Sept 16, 2025]. [Preprint]. https://doi.org/10.21203/rs.3.rs-239294/v1

23.al-Rowaih A, Björkengren A, Egund N, Lindstrand A, Wingstrand H, Thorngren KG. Size of osteonecrosis of the knee. Clin Orthop Relat Res. 1993;287(287):68-75.

24.Infante Calvo C, Barahona Vásquez M, Palet Bonell M, Zamorano Cadenas Á. Traumatología de la Rodilla: traumatología y ortopedia de la rodilla enfocado en residentes de la especialidad y traumatólogos generales. Chile: Departamento de Ortopedia y Traumatología, Facultad de Medicina, Universidad de Chile; 2021. https://doi.org/10.34720/agz2-hw86.

25.Anzillotti G, Öttl FC, Franceschi C, Conte P, Bertolino EM, Lipina M, et al. No Significant Differences between Bisphosphonates and Placebo for the Treatment of Bone Marrow Lesions of the Knee: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Clin Med. 2024;13(13):3799. https://doi.org//10.3390/jcm13133799 PMID: 38999364; PMCID: PMC11242668.

26.Ververidis AN, Paraskevopoulos K, Keskinis A, Petkidis GI, Tilkeridis K. The efficacy and safety of bisphosphonates in patients with bone marrow edema syndrome/transient osteoporosis: A systematic literature review. J Orthop. 2020;22:592-7. https://doi.org/10.1016/j.jor.2020.11.011 PMID: 33299271; PMCID: PMC7691669.

27.Meier C, Kraenzlin C, Friederich NF, Wischer T, Grize L, Meier CR, et al. Effect of ibandronate on spontaneous osteonecrosis of the knee: a randomized, double-blind, placebo-controlled trial. Osteoporos Int. 2014;25(1):359-66. https://doi.org/10.1007/s00198-013-2581-5 PMID: 24264372.

28.Sansone V, Romeo P, Lavanga V. Extracorporeal Shock Wave Therapy Is Effective in the Treatment of Bone Marrow Edema of the Medial Compartment of the Knee: A Comparative Study. Med Princ Pract. 2017;26(1):23-9. https://doi.org/10.1159/000452836 PMID: 27784022; PMCID: PMC5588340.

29.Gao F, Sun W, Li Z, Guo W, Wang W, Cheng L, et al. Extracorporeal shock wave therapy in the treatment of primary bone marrow edema syndrome of the knee: a prospective randomised controlled study. BMC Musculoskelet Disord. 2015;16(1):379. https://doi.org/10.1186/s12891-015-0837-2 PMID: 26637992; PMCID: PMC4670725.

30.Wheatley BM, Nappo KE, Christensen DL, Holman AM, Brooks DI, Potter BK. Effect of NSAIDs on Bone Healing Rates: A Meta-Analysis. J Am Acad Orthop Surg. 2019;27(7):e330-6. https://doi.org/10.5435/JAAOS-D-17-00727 PMID: 30260913.

31.Ali MU, Usman M, Patel K. Effects of NSAID use on bone healing: A meta-analysis of retrospective case-control and cohort studies within clinical settings. Trauma. 2020;22(2):94-111. https://doi.org/10.1177/1460408619886211

32.World Medical Association. World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Participants. JAMA. 2025;333(1):71-74. https://doi.org/10.1001/jama.2024.21972 PMID: 39425955.

33.Colombia. Ministerio de Salud. Resolución 8430 de 1993 (octubre 4): Por la cual se establecen las normas científicas, técnicas y administrativas para la investigación en salud [Internet]. Bogotá D.C.; october 4 1993 [cited 2026 Feb 12]. Available from: https://bit.ly/31gu7do.

34.Aglietti P, Insall JN, Buzzi R, Deschamps G. Idiopathic osteonecrosis of the knee. Aetiology, prognosis and treatment. J Bone Joint Surg Br. 1983;65(5):588-97. https://doi.org/10.1302/0301-620X.65B5.6643563 PMID: 6643563.

35.Marti CB, Rodriguez M, Zanetti M, Romero J. Spontaneous osteonecrosis of the medial compartment of the knee: a MRI follow-up after conservative and operative treatment, preliminary results. Knee Surg Sports Traumatol Arthrosc. 2000;8(2):83-8. https://doi.org/10.1007/s001670050191 PMID: 10795669.

36.Fujita S, Arai Y, Honjo K, Nakagawa S, Kubo T. A Case of Spontaneous Osteonecrosis of the Knee with Early and Simultaneous Involvement of the Medial Femoral Condyle and Medial Tibial Plateau. Case Rep Orthop. 2016;2016:2574975. https://doi.org/10.1155/2016/2574975 PMID: 27242941; PMCID: PMC4868907.

37.Giannini S, Mazzotti A, Arceri A. Osteonecrosis of the knee: a concise review of the current literature. Int J Bone Frag. 2022;2(1):11-5. https://doi.org/10.57582/IJBF.220201.011

38.Bouvard B, Annweiler C, Legrand E. Osteoporosis in older adults. Joint Bone Spine. 2021;88(3):105135. https://doi.org/10.1016/j.jbspin.2021.105135 PMID: 33486108.

39.Akamatsu Y, Mitsugi N, Hayashi T, Kobayashi H, Saito T. Low bone mineral density is associated with the onset of spontaneous osteonecrosis of the knee. Acta Orthop. 2012;83(3):249-55. https://doi.org/10.3109/17453674.2012.684139 PMID: 22537352; PMCID: PMC3369150.

40.Chambers C, Craig JG, Zvirbulis R, Nelson F Spontaneous Osteonecrosis of Knee After Arthroscopy Is Not Necessarily Related to the Procedure. Am J Orthop (Belle Mead NJ). 2015;44(6):E184-9. PMID: 26047003.

41.Nelson FR, Craig J, Francois H, Azuh O, Oyetakin-White P, King B. Subchondral insufficiency fractures and spontaneous osteonecrosis of the knee may not be related to osteoporosis. Arch Osteoporos. 2014;9:194. https://doi.org/10.1007/s11657-014-0194-z PMID: 25234658.

42.Yasuda T, Ota S, Fujita S, Onishi E, Iwaki K, Yamamoto H. Association between medial meniscus extrusion and spontaneous osteonecrosis of the knee. Int J Rheum Dis. 2018;21(12):2104-11. https://doi.org/10.1111/1756-185X.13074

43.Hussain ZB, Chahla J, Mandelbaum BR, Gomoll AH, LaPrade RF. The Role of Meniscal Tears in Spontaneous Osteonecrosis of the Knee: A Systematic Review of Suspected Etiology and a Call to Revisit Nomenclature. Am J Sports Med. 2019;47(2):501-507. https://doi.org/10.1177/0363546517743734 PMID: 29253348.

44.Yamagami R, Taketomi S, Inui H, Tahara K, Tanaka S. The role of medial meniscus posterior root tear and proximal tibial morphology in the development of spontaneous osteonecrosis and osteoarthritis of the knee. Knee. 2017;24(2):390-5. https://doi.org/10.1016/j.knee.2016.12.004 PMID: 28169099.