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Current Trends and Variations in the Treatment of Unicameral Bone Cysts of the Humerus

A Survey of EPOS and POSNA Members

Farr, Sebastian MD*; Balacó, Inês Maria Spencer MD; Martínez-Alvarez, Sergio MD; Hahne, Julia ScD§; Bae, Donald S. MD

Author Information
Journal of Pediatric Orthopaedics: January 2020 - Volume 40 - Issue 1 - p e68–e76
doi: 10.1097/BPO.0000000000001376
  • Open

Abstract

Unicameral bone cysts (UBCs) are the most common tumor-like lesions in the immature skeleton, most commonly appearing in the humerus and proximal femur. Although many are found incidentally, active, expanding cysts may predispose to the development of pathologic fractures that need further treatment.1

A variety of treatment methods have been described for UBCs.2,3 The most common surgical procedures include curettage with or without bone grafting (eg, autologous bone graft, bone substitutes4–6 or rarely recombinant bone morphogenetic protein [BMP]7), percutaneous decompression,8,9 corticosteroid injection10 or autologous bone marrow injection.11 However, many of these methods have been shown to have high rates of recurrence,12 especially with incomplete curettage13 or when rapid venous outflow is noted on cystography.14 Local reactions have also been reported.7 Moreover, a distance of >2 cm to the growth plate has generally been linked to improved outcomes.15

Treatment of UBCs in the humerus (and femur) using a combined steroid, bone matrix and bone marrow injection has been suggested.16 In addition, intramedullary nailing has been advocated in cases with or without pathologic fracture to decompress the cyst and confer stability of the affected bone.17 However, uniform indications for surgical treatment have not been established, and to the best of our knowledge, no consensus has been reached on timing of surgery or optimal technique. Anecdotally, surgery is most indicated in cases of persistent pain, pathologic fracture,18 or need for tissue diagnosis.

Large-scale surveys are valuable tools to assess indications, treatment approaches and surgical methods among surgeons in different centers and countries. To this end, members of the European Pediatric Orthopedic Society (EPOS) and Pediatric Orthopedic Society of North America (POSNA) were surveyed to characterize current treatment preferences.

METHODS

An online questionnaire, created by 4 fellowship-trained pediatric orthopedic surgeons, was sent to all registered EPOS and POSNA members (including active and candidate members). The questionnaire was pretested in a convenience sample of ten pediatric orthopaedic surgeons working at the authors’ institutions. A waiver of Institutional Review Board approval was granted by the principal investigator’s institution because of the nature of the study. The study was approved by the EPOS Scientific Committee, EPOS Board, and the POSNA Evidence Based Practice Committee. An invitation reminder was sent after 4 weeks by both societies.

The survey consisted of 45 questions related to the diagnosis, treatment, and follow-up of patients with UBCs of the humerus. Respondents were first asked whether they treat UBCs at all or not. If declined, the survey was automatically terminated to avoid gathering information that does not reflect actual clinical practice and experience. All those who responded “yes” were asked to answer (1) provider demographic questions (eg, experience, years in practice), (2) diagnostic preferences (eg, when to obtain a biopsy, magnetic resonance imaging [MRI]), and (3) treatment preferences for incidental, painful, fractured and/or therapy-refractory/recurrent humeral UBCs. Specific questions related to the treatment of pathologic proximal humeral and humeral diaphyseal fractures were also included, as were 2 clinical scenarios. The survey included binary questions (yes/no), single and multiple choice (select all that apply) answers, and open text boxes.

Descriptive statistics were calculated based upon respondents who reported they actively care for patients with UBCs. Means, standard deviation, and interquartile ranges were calculated. Subanalysis was performed stratified according to whether respondents (1) are EPOS or POSNA members, (2) treat more or less than 10 humerus UBCs per year, (3) are more or less than 10 years in clinical practice, and (4) have more or less than 10% of upper limb surgery in their daily practice. The data was screened for potential clinically relevant differences. Thereafter, depending on parametric or nonparametric distribution, student´s tests, Mann-Whitney U test or χ2 tests were computed.

RESULTS

Demographics

The survey was electronically distributed to 427 EPOS and 1270 POSNA members; 444 participants from 28 countries responded to the survey (26% overall response rate), of which 132 were EPOS (31% EPOS response rate) and 292 POSNA members (23% POSNA response rate); 28 respondents were members of both societies; 400 (90%) of the 444 respondents stated they treated children with UBCs (Table 1).

TABLE 1
TABLE 1:
Demographic Details of 400 Study Respondents*

Diagnostic Preferences

Overall, the preferred diagnostic modalities to confirm the diagnosis of a UBC in the humerus were radiographs (88%), MRI in cases of questionable diagnosis (58%), or CT scan (8%). Only 10% of respondents prefer obtaining an MRI in every single UBC case. Reasons for additional radiographic investigation are shown in Table 2.

TABLE 2
TABLE 2:
Most Common Reasons for Additional Imaging (N=278)

In painless, incidental UBCs, advanced imaging (MRI/CT) is never (50%), sometimes (43%) or always (7%) preferred. This rate, however, increases in painful cases to 9%, 58%, and 33%, respectively, and in fractured UBCs to 36%, 54%, and 10%, respectively.

Bone biopsy is mainly preferred in cases of unclear diagnosis/imaging (64%) or pathologic fracture (3%); 8% of respondents reported they always perform a biopsy. Most common reasons for biopsy are shown in Table 3.

TABLE 3
TABLE 3:
Most Common Reasons for Biopsy (N=234)

Treatment Preferences

For a painless, incidentally found UBC with a low fracture risk 67% prefer no treatment at all (with regular follow-ups), 18% advise sports restriction for certain activities (with follow-up), 9% would do no follow-up at all, and 5% would recommend surgery (including injections). In cases of painless UBCs with high fracture risk, 53% recommend surgery, 32% sports restriction, 13% just follow-up. The age at diagnosis was found to have no effect on treatment in 60% of respondents. Other relevant influencing factors are shown in Figure 1.

FIGURE 1
FIGURE 1:
Factors influencing decision for surgical treatment among survey respondents. UBC indicates unicameral bone cysts.

In total, 71% of respondents would treat painful UBC in children under 10-12 years of age with surgery, compared with observation with sports restriction (22%) or observation alone (8%). The most common techniques and/or materials are curettage (45%), artificial bone substitutes (37%), corticosteroid injection (29%) or intramedullary stabilization (eg, rodding; 24%; Table 4). Less common methods include bone marrow injection (18%), autologous bone grafts (9%), homologue bone grafts (5%), or BMP (3%). Techniques to address recurrent cysts are shown in Table 4.

TABLE 4
TABLE 4:
Surgical Treatment Details of the Respondents

In children over 10 to 12 years of age, only half as many respondents favored observation alone (4%). Fewer surgeons choose corticosteroid injection (22%) for this older age group as a primary treatment (Table 4).

Fractured, nondisplaced proximal humerus UBCs are treated nonoperatively by the vast majority (94%); when surgery is done, curettage (25%) and rodding (27%) are preferred (Table 4).

Fractured, mildly displaced (Neer-Horwitz grades I and II) proximal humerus UBCs are more often treated nonoperatively (eg, sling and swathe; 91%) than surgically (9%). In contrast, fractured, severely displaced (Neer-Horwitz grades III and IV) proximal humerus UBCs are more often treated surgically (40% vs 36%), with 24% favoring closed reduction techniques. Most common surgical techniques for severely displaced pathologic fractures include intramedullary stabilization (41%) and open reduction with plate fixation (ORIF; 25%) (Table 4).

Mildly displaced pathologic humerus shaft fractures are preferably treated nonoperatively (83%); when surgery is performed, intramedullary stabilization (36%) and curettage (26%) are preferred. In contrast, severely displaced humerus shaft fractures are preferably treated surgically (63%) by intramedullary stabilization (60%), curettage (33%), ORIF (20%), and/or bone substitutes (17%). Surgeons with >10 years of experience tend to (1) treat severely displaced pathologic shaft fractures less often surgically (59%) than those with less than ten years of experience (71%; P=0.041); (2) remove the implants later (P=0.001); and (3) have seen more often spontaneous cyst resolution (P=0.029).

Comparison Between EPOS and POSNA members

There were no statistically significant differences between EPOS and POSNA members with regards to frequency of routine biopsy (P=0.401). However, EPOS members order significantly more advanced imaging studies in painless (P<0.0001), nonfractured painful (P=0.002) and fractured (P<0.0001) UBCs to characterize the cyst and fracture risk (Fig. 2).

FIGURE 2
FIGURE 2:
Diagnostic preferences (advanced imaging yes/no) among EPOS and POSNA members for painless (A), painful (B), and fractured unicameral bone cysts (C). There were statistically significant differences among all subgroups shown (A, χ2 test, χ2=34.502, P<0.0001; B, Mann-Whitney U test, U=8756.0, P=0.002; C, Mann-Whitney U test, U=5784.0, P<0.0001). EPOS indicates European Pediatric Orthopedic Society; POSNA, Pediatric Orthopedic Society of North America.

EPOS members also tend to treat painless UBCs more often surgically (10.2% vs. 2.8%; P=0.13) than POSNA members. No differences were seen in treatment of painful UBCs (68.1% vs. 71.6%; P=0.84). In nondisplaced proximal humerus fractures, EPOS members again tend to prefer surgical treatment significantly more often than POSNA members (12.2% vs. 3.9%; P=0.030; Fig. 3). The same behavior was noted for Neer-Horwitz grade I & II (21.0% vs. 4.9%; P<0.0001) and grade III & IV (66.7% vs. 29.7%; P<0.0001). In addition, mildly displaced humerus shaft fractures (36.6% vs. 8.8%; P<0.0001) as well as severely displaced ones (87.8% vs. 52.7%; P<0.0001) are more often surgically treated by EPOS members (Fig. 4).

FIGURE 3
FIGURE 3:
Treatment preferences among EPOS and POSNA members for painless (A), painful (B), and fractured undisplaced unicameral bone cysts (C). There were statistically significant differences among subgroups shown in A (χ2 test, χ2=19.411, P=0.013) and C (χ2 test, χ2=7.030, P=0.030) but not in B (χ2 test, χ2=8.230, P=0.084). EPOS indicates European Pediatric Orthopedic Society; FU, follow-up; POSNA, Pediatric Orthopedic Society of North America.
FIGURE 4
FIGURE 4:
Treatment preferences among EPOS and POSNA members for Neer-Horwitz grade I and II (A), grade III and IV (B), and mildly (C) and severely displaced (D) humerus shaft fractures with unicameral bone cysts, respectively. There were statistically significant differences among all subgroups shown (A, χ2 test, χ2=17.943, P<0.0001; B, χ2 test, χ2=36.652, P<0.0001; C, χ2 test, χ2=33.095, P<0.0001; D, χ2 test, χ2=32.171, P<0.0001). EPOS indicates European Pediatric Orthopedic Society; POSNA, Pediatric Orthopedic Society of North America.

There are no significant differences with regards to implant removal (P=0.785). EPOS members anecdotally observed more often spontaneous UBC resolution after skeletal maturity (“often” 17.1% vs. 10.8%; “sometimes” 46.3% vs. 36.3%; P=0.007).

Follow-up

In patients treated with intramedullary implants, 2% of respondents remove the implants within 6 months, 35% prefer to wait 6 to 12 months postoperatively, and 31% later than 12 months postoperatively; 19% never remove the implants. Moreover, we asked whether the surgeons have ever observed spontaneous cyst resolution after skeletal maturity. With this regards, most responded “sometimes” (39%), followed by “rarely” (27%), “never” (21%) and “often” (13%).

DISCUSSION

In this international survey of over 400 pediatric orthopaedic surgeons, therapeutic choices for UBCs varied, with no consensus regarding optimal evaluation or treatment. This variation, combined with limited information regarding healing rates, makes selection of the appropriate treatment for UBCs challenging.

The pathoetiology of UBCs is still unknown, limiting the development of targeted treatment strategies. The historic assumption that most UBCs will resolve with skeletal maturity has been challenged by longer follow-up studies.19 Despite the favorable results reported of injections with bone substitutes, methodological issues make interpretation of those results difficult, and there are still concerns about systemic effects, including embolization.5,20–22 Currently, steroids are still the only evidence-based option for treatment of UBCs.2,23–25 There has been growing enthusiasm for simple cyst decompression without grafting (percutaneous curettage and decompression with flexible intramedullary nail).8,18,26,27 The multimodal combination of all the minimally invasive techniques seems to be an emerging trend for treatment; this combination consists of opening the cyst wall, filling of the defect with a bone substitute, and biological treatment of the cyst membrane, with or with internal fixation.3,6,16,22,25,28–31

A recent systematic review and meta-analysis assessed the results of 497 humerus UBCs treated by 16 different modalities.32 Injection with bone marrow and demineralized bone matrix (BMA/DBM) was successful in 100% (28/28) of patients treated, comparing favorably to the 81% (86/106) success rate with steroid injection and 22% (12/53) success rate with nonoperative treatment. However, there was insufficient evidence to recommend BMA/DBM over steroid injection or a more invasive open surgery.

Kadhim et al12 evaluated three different treatments: conservative, injection with mehylprednisolone (MPA) or bone marrow, and open surgery with curettage and bone grafting. In contrast to other reports, the observed healing rate of humerus UBCs with observation was higher in younger children, and failure to heal was observed more often with MPA injection compared with bone marrow injection. Moreover, Gundle et al reported the outcomes of injecting bone marrow aspirate and demineralized bone matrix (BMA/DBM) for the treatment of 51 patients with proximal humerus UBCs.33 Of 51 patients initially treated with BMA/DBM, only 11 (22%) healed with single injection, and 67% were cumulatively successful after 3 injections. Despite a multitude of different studies performed on this topic, it is though not fully clear whether radiologic healing or even pain relief itself should be the main purpose of cyst surgery. Most studies define radiographic healing as “the” successful outcome; however, from a clinical perspective pain relief, return to full activities and incidence of refracture may be outcome factors of equal importance.

In general, cyst size, presence of symptoms, and risk of pathologic fracture influenced the treatment decision the most. According to our study, UBCs are mostly being treated (67%) nonoperatively as long as the fracture risk is deemed low. For this reason, in the setting of a large symptomatic cyst at risk for fracture, surgery should be considered—even if the natural history may be one of spontaneous resolution—to avoid the morbidity of pain and fracture. With regards to incidental UBCs, we observed a higher rate and tendency for surgical treatment among EPOS members. Painful UBCs, which may be caused by for example cyst expansion or an impending fracture, are treated operatively in 71%, with curettage, artificial bone substitution, corticosteroid injection, and intramedullary stabilization being the most preferred modalities.

In addition, the results of our study showed that native radiographs are typically sufficient for diagnosis; advanced imaging or biopsy are uncommonly performed and may not be necessary for diagnostic purposes. However, in situations in which the diagnosis is unclear, as may be seen with concomitant pathologic fracture, providers should not hesitate to utilize additional diagnostic modalities to establish the diagnosis of a benign cyst and to distinguish pathologic UBC fracture from infection or malignancy.

Pathologic fractures of the humerus are quite frequent, and UBC and other benign lesions of the humerus are often first diagnosed coincident to a pathologic fracture. According to the literature, the majority of pediatric proximal and diaphyseal humerus fractures may be successfully treated nonoperatively. In some instances, the cyst will spontaneously resolve during or after fracture healing.34 More commonly, the UBC may be observed with anticipation of progression from active to quiescent to involutional stages, with resolution by skeletal maturity. Acute surgical treatment for pathologic humeral fractures is quite rare.

With this regards our survey showed that nondisplaced and mildly displaced proximal humerus fractures, and mildly displaced humerus shaft fractures are currently being treated nonoperatively in the majority of cases, with relative even distribution (36% conservative, 40% surgery) for severely displaced proximal humerus fractures, and a tendency for surgical restoration in severely displaced shaft fractures (63%). Again, the fracture pattern—not the presence of the UBC—drives decision-making regarding treatment. Interestingly, more experienced surgeons (>10 y experience) treated severely displaced shaft fractures less often surgically. At this point, we can only speculate if this is because they are more confident that resolution occurs or because they are less familiar with surgical options. Finally, EPOS members showed a clear preference for surgical treatment not only for incidental UBCs but also among the different fractures sites compared with their POSNA colleagues. Potential reasons for this include familiarity with less invasive techniques, less confidence in spontaneous resolution, and greater concern for late deformity or recurrent pathological fracture.

Another interesting observation worth mentioning is that, although many surgeons believe UBCs resolve at maturity, almost half of all members have never or rarely ever seen spontaneous cyst resolution. Whether this could be because of incomplete follow-up or perhaps erroneous belief in spontaneous resolution remains unclear. Moreover, our results have shown that most surgeons prefer to remove hardware at 6 to 12 months or later than 12 months after surgery. As the authors have seen difficult or frustrane hardware removal in cases with intramedullary hardware in situ for >12 months, we often opt for the 6 to 12 months postoperative interval. However, it should be noted that cyst resolution or healing should have at least partially occurred by that time, otherwise the hardware should be kept in situ for a longer period.

This study has several limitations. The response rate (26%) was somewhat low, though consistent with recent EPOS and POSNA surveys and prior published reports.35 Variation of treatment may in reality be higher since we do not know preferences of non-EPOS/POSNA members throughout the world. Finally, the information provided reveals current practice preferences and treatment choices; however, the most frequent treatment options may not necessarily be the most efficacious. Further prospective studies are needed to determine which of these methods are truly superior over the others.

To summarize, there is great variation among EPOS and POSNA members with regards to the diagnosis and treatment of UBCs in the humerus. Although some consensus on general treatment principles is seen (eg, incidental UBCs, implant removal, and diagnosis), specific surgical treatment indications vary between EPOS and POSNA members and within the whole cohort of respondents. Prospective randomized-controlled studies are needed to shed more light on the outcomes of the different surgical approaches compared with nonoperative strategies.

ACKNOWLEDGMENTS

The authors thank all EPOS and POSNA members who participated in this survey.

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Keywords:

unicameral bone cyst; humerus cyst; juvenile bone cyst; humerus fracture; corticosteroid injection; intramedullary stabilization; curettage; bone graft

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