Orthopedics

Radiologic Case Study 

Radiologic Case Study

Bryan Garcia, MS; Laura W. Bancroft, MD; J. Dean Cole, MD

Abstract

A 50-year-old woman presented with left hip pain.

Your diagnosis?

Radiograph (A), computed tomography scan (B), and magnetic resonance image (C).

Figure: Radiograph (A), computed tomography scan (B), and magnetic resonance image (C).…

Figure: Radiograph (A), computed tomography scan (B), and magnetic resonance image (C).

Multiple Myeloma With Cadaveric Graft Reconstruction of the Ilium

Mr Garcia is from the Florida State University College of Medicine, Tallahassee, Dr Bancroft is from the Department of Radiology, Florida Hospital, and Dr Cole is from the Fracture Care Center, Orlando, Florida.

Mr Garcia and Drs Bancroft and Cole have no relevant financial relationships to disclose.

Correspondence should be addressed to: Laura W. Bancroft, MD, Department of Radiology, Florida Hospital, 600 E Rollins, Orlando, FL (laura.bancroft.md@flhosp.org).
 

A 50-year-old woman with a history of myeloma presented with left hip pain (Figure 1). She was status post radiation therapy for a large left innominate bone plasmacytoma. She sustained a pathologic acetabular fracture as a result of this lytic lesion and underwent excision of the pelvic tumor with extensive surgical reconstruction, including total hip arthroplasty and bone allograft.

Figure 1: Anteroposterior radiograph of the pelvic showing an expansile lytic lesion involving the left ilium (arrows), with superior migration of the femoral head due to acetabular involvement (A). Axial computed tomography scan with contrast showing the expansile mass (asterisk) involving the entire ilium, with cortical destruction (B). Coronal T1-weighted (C) and fast spin echo T2-weighted (D) magnetic resonance images showing the mass (asterisks), which is isointense to skeletal muscle on the T1-weighted image and hyperintense on the T2-weighted image.

Myeloma is a clonal B-cell neoplasm resulting in the overproduction of monoclonal immunoglobulins commonly involving, but not limited to, the bone marrow.1 Myeloma accounts for 1% of all malignancies and approximately 10% of all hematologic malignancies, with greatest predominance during the seventh decade of life and an average age at diagnosis of 60 years.2

Management and treatment of myeloma is based on staging using the Durie-Salmon PLUS staging system, which takes into account the patient’s hemoglobin, serum calcium, radiographic evidence of lytic bone lesions, M-protein level, and renal function.3 Prognosis is highly variable, with survival ranging from months to up to 10 years.4 Recently, an expanded role for imaging has evolved in the staging of disease and in assessing for early response to therapy.

Clinical presentation of patients with myeloma varies from incidental findings on routine blood tests to life-threatening disease resulting from the effects of bone marrow infiltration by the malignant plasma cells. Classically, patients present with bone pain and fatigue.5 Pathologic fractures due to lytic destruction of bone may occur, as may renal insufficiency secondary to the hypercalcemia and deposition of the monoclonal light chains in the collecting tubules.6 Other symptoms include infections, increased bleeding, nonspecific radicular pain, and hyperviscosity syndrome.

Overproduction of the monoclonal M-protein produced by the abnormal cells can be detected on electrophoresis of the blood or urine.7 Lytic (and occasionally sclerotic) bone lesions can be detected on imaging studies, and bone marrow biopsy with cytogenetic analysis can confirm diagnosis and identify specific karyotype alterations suggestive of a grave prognosis.8

Traditionally, staging of myeloma has been accomplished using the International Scoring System (ISS) and the Durie-Salmon system. Recently, the Durie-Salmon system was updated to include magnetic resonance imaging (MRI) or 2-deoxy-2-(18F)fluoro-D-glucose positron emission tomography (FDG-PET) and is now known as the Durie-Salmon PLUS system.9 The ISS is not a true staging system that quantifies tumor burden, rather, it is used only for prognostication in patients who meet all criteria for having myeloma. This accounts for the fact that other disease processes can result in elevated levels of β2-microglobulin and renal dysfunction without patients having myeloma

The Case:

A 50-year-old woman presented with left hip pain.

Your diagnosis?

Radiograph (A), computed tomography scan (B), and magnetic resonance image (C).

Figure: Radiograph (A), computed tomography scan (B), and magnetic resonance image (C).

Diagnosis:

Multiple Myeloma With Cadaveric Graft Reconstruction of the Ilium

Mr Garcia is from the Florida State University College of Medicine, Tallahassee, Dr Bancroft is from the Department of Radiology, Florida Hospital, and Dr Cole is from the Fracture Care Center, Orlando, Florida.

Mr Garcia and Drs Bancroft and Cole have no relevant financial relationships to disclose.

Correspondence should be addressed to: Laura W. Bancroft, MD, Department of Radiology, Florida Hospital, 600 E Rollins, Orlando, FL (laura.bancroft.md@flhosp.org).
 

A 50-year-old woman with a history of myeloma presented with left hip pain (Figure 1). She was status post radiation therapy for a large left innominate bone plasmacytoma. She sustained a pathologic acetabular fracture as a result of this lytic lesion and underwent excision of the pelvic tumor with extensive surgical reconstruction, including total hip arthroplasty and bone allograft.

Anteroposterior radiograph of the pelvic showing an expansile lytic lesion involving the left ilium (arrows), with superior migration of the femoral head due to acetabular involvement (A). Axial computed tomography scan with contrast showing the expansile mass (asterisk) involving the entire ilium, with cortical destruction (B). Coronal T1-weighted (C) and fast spin echo T2-weighted (D) magnetic resonance images showing the mass (asterisks), which is isointense to skeletal muscle on the T1-weighted image and hyperintense on the T2-weighted image.

Figure 1: Anteroposterior radiograph of the pelvic showing an expansile lytic lesion involving the left ilium (arrows), with superior migration of the femoral head due to acetabular involvement (A). Axial computed tomography scan with contrast showing the expansile mass (asterisk) involving the entire ilium, with cortical destruction (B). Coronal T1-weighted (C) and fast spin echo T2-weighted (D) magnetic resonance images showing the mass (asterisks), which is isointense to skeletal muscle on the T1-weighted image and hyperintense on the T2-weighted image.

Myeloma is a clonal B-cell neoplasm resulting in the overproduction of monoclonal immunoglobulins commonly involving, but not limited to, the bone marrow.1 Myeloma accounts for 1% of all malignancies and approximately 10% of all hematologic malignancies, with greatest predominance during the seventh decade of life and an average age at diagnosis of 60 years.2

Management and treatment of myeloma is based on staging using the Durie-Salmon PLUS staging system, which takes into account the patient’s hemoglobin, serum calcium, radiographic evidence of lytic bone lesions, M-protein level, and renal function.3 Prognosis is highly variable, with survival ranging from months to up to 10 years.4 Recently, an expanded role for imaging has evolved in the staging of disease and in assessing for early response to therapy.

Clinical Findings

Clinical presentation of patients with myeloma varies from incidental findings on routine blood tests to life-threatening disease resulting from the effects of bone marrow infiltration by the malignant plasma cells. Classically, patients present with bone pain and fatigue.5 Pathologic fractures due to lytic destruction of bone may occur, as may renal insufficiency secondary to the hypercalcemia and deposition of the monoclonal light chains in the collecting tubules.6 Other symptoms include infections, increased bleeding, nonspecific radicular pain, and hyperviscosity syndrome.

Overproduction of the monoclonal M-protein produced by the abnormal cells can be detected on electrophoresis of the blood or urine.7 Lytic (and occasionally sclerotic) bone lesions can be detected on imaging studies, and bone marrow biopsy with cytogenetic analysis can confirm diagnosis and identify specific karyotype alterations suggestive of a grave prognosis.8

Clinical Staging and Prognosis

Traditionally, staging of myeloma has been accomplished using the International Scoring System (ISS) and the Durie-Salmon system. Recently, the Durie-Salmon system was updated to include magnetic resonance imaging (MRI) or 2-deoxy-2-(18F)fluoro-D-glucose positron emission tomography (FDG-PET) and is now known as the Durie-Salmon PLUS system.9 The ISS is not a true staging system that quantifies tumor burden, rather, it is used only for prognostication in patients who meet all criteria for having myeloma. This accounts for the fact that other disease processes can result in elevated levels of β2-microglobulin and renal dysfunction without patients having myeloma (eg, patients with monoclonal gammopathy of undetermined significance and comorbid diabetes mellitus).10 For this reason, it is recommended that the ISS be used in conjunction with the Durie-Salmon PLUS system.

A relative paucity of literature exists on the new Durie-Salmon PLUS staging system; however, recent studies have identified that a significant number of patients will be understaged using the previous system, which used radiographs for the skeletal survey compared with those staged using the Durie-Salmon PLUS system; this may result in patients not being managed aggressively enough.9 This article further evaluates the current use of imaging for the skeletal survey.

Although not included in staging, cytogenetics is commonly used for further prognostication driving therapeutic decision making. Patients whose tumors show deletion of chromosome 13 or certain translocations, including t(4,14) and t(14,16), are considered to have high-risk myeloma and should be managed more aggressively.8

Imaging

Historically, a complete skeletal survey using radiography was undertaken at diagnosis with myeloma (Figure 1A). Approximately 80% of patients will have radiographic evidence of skeletal involvement at diagnosis, most commonly involving the vertebrae but also seen in the ribs, skull, shoulder, pelvis, and long bones.11 This imaging modality is more sensitive than MRI in detecting cortical bone lesions; however, 30% to 50% of bone mineral density must be lost for it to be evident on radiographs. Furthermore, radiographs have a high false-negative rate of up to 67%, which leads to understaging the disease, and lack the ability to accurately address bone marrow involvement.12 Lastly, due to the multiple positions required to conduct the skeletal survey, this method proves difficult for patients suffering bone pain due to their myeloma.

Computed tomography (CT) has not been widely used for screening purposes due to the large amount of radiation required.13 Nevertheless, CT has proven to have a higher sensitivity at detecting the lytic lesions of myeloma compared with radiography (Figure 1B). Furthermore, CT has the added advantage of showing potential bone instability and extramedullary areas of myeloma.13

Whole-body MRI has become the most sensitive modality for detection of myeloma involvement of bone.14 It has the ability to provide exquisite visualization of the bone marrow without radiation exposure (Figures 1C, D). Studies have shown that the number and pattern of the skeletal lesions detected by MRI provide excellent prognostic information and correlate with overall survival; for these reasons, it has been included in the Durie-Salmon PLUS system of staging myeloma.3 Similar to CT, MRI also requires a prolonged period of time to show improvement during treatment; however, diffusion-weighted imaging is being studied as an imaging method to follow successful therapy. Treated myelomatous lesions show different imaging characteristics as they transition from solid lesions of active disease with dense tumor cell clusters to cystic defects filled with fluid or debris during remission or after successful treatment.15

The FDG-PET uses labeled fluorodeoxyglucose to indicate tumor burden because metabolically active tumor cells have a propensity to uptake this glucose analogue. Studies using this imaging method are ongoing, with the hope that they will better detect early stages of bone marrow involvement in patients thought to have solitary plasmacytomas.16 The most important advantage of FDG-PET is its ability to distinguish active myeloma from monoclonal gammopathy of undetermined significance.16 Furthermore, unlike MRI, which requires a prolonged time interval prior to noticeable changes on imaging, this imaging modality can be used to demonstrate successful treatment because fluorodeoxyglucose uptake decreases within the myelomatous lesion rapidly following successful therapy.17 However, whole-body MRI performed better overall than did FDG-PET in the assessment of disease activity in a study by Shortt et al,18 having a higher sensitivity (68% vs 59%, respectively) and specificity (83% vs 75%, respectively).

Medical Management

Therapeutic decision making is dictated by the patient’s age, disease stage, performance status, and comorbidities at presentation. Recently, initial chemotherapy with hematopoietic stem cell transplant has been used with increasing success, but it is typically reserved for patients younger than 65 years.19 In patients who are candidates for allogeneic stem cell transplant, the potential for a cure exists. However, most patients are not candidates for this and receive an autologous stem cell transplant using their own stem cells. Although autologous stem cell transplant is not curative, it has been shown to improve overall survival.19 In patients who receive stem cell transplant, the most well-studied induction chemotherapy regimens use thalidomide-dexamethasone and lenalidomide-dexamethasone, and recent therapies have included the protease inhibitor bortezomib.20 In patients older than 65 years who are not eligible for stem cell transplant, the most common regimens use melphalan, thalidomide, and prednisone.21

Patients who are eligible for autologous stem cell transplant should not receive melphalan or other alkylating agents because this will make collection of healthy stem cells difficult.21 With regard to maintenance therapy, the role of these agents is not fully understood, and ongoing trials seek to better understand their use. It is important to understand that the natural course of myeloma is one of relapse, and these same therapeutics are used in patients with relapse, often in conjunction with cyclophosphamide.20

In addition to controlling the tumor burden with these agents, patients must be monitored for signs of renal disease, diabetes mellitus, and osteoporosis. Hypercalcemia and deposition of light chains in the renal tubules can result in acute renal failure.22 Treatment of impaired renal function includes intravenous fluids, dialysis, and allopurinol to decrease uric acid. The high doses of corticosteroids required for therapy can result in uncontrolled glucose levels and osteoporosis.23 As the microenvironment of bone marrow has become better understood, it has become apparent that bisphosphonates can be used to improve osteoblastic bone anabolism.24

Patients being treated with chemotherapy are at an increased risk for infection, as are patients with myeloma due to inappropriate production of dysfunctional immunoglobulins.25 For this reason, all patients should receive the pneumococcal vaccine and influenza vaccine, and in some cases should receive trimethoprim-sulfamethoxazole daily.25

Surgical Management

Skeletal lesions are present in approximately 60% of patients with a diagnosis of myeloma and may result in pathologic fractures. The portions of the skeleton most commonly affected by these lytic lesions are the vertebrae and long bones. The decision to stabilize such lesions is made by the orthopedic surgeon, with the general rule being that surgical fixation is required if more than 50% of cortical bone loss has occurred.

A dearth of literature exists regarding the surgical management of myeloma of long bones. A recent retrospective study of 22 patients showed that the most common site of pathologic fracture of the long bones was in the femur and demonstrated a low implant failure rate and no evidence of tumor dissemination intraoperatively.26 The authors recommended open reduction and internal fixation with cement augmentation for patients amenable to surgery. However, the study demonstrated a low rate (30%) of union, which the authors believed may have been secondary to postoperative radiation therapy or insufficient bone healing caused by tumor infiltration.26

The spine is particularly susceptible to pathologic fracture due to myelomatous lesions.27 For this reason, a significant amount of literature exists regarding the use of kyphoplasty and vertebroplasty for the treatment of myeloma of the spine. The primary indications for these procedures in myeloma are pain control and the prevention or improvement of neurological deficits in patients with a life expectancy of more than 3 months.14 These procedures are minimally invasive and are used for the stabilization of fractures secondary to osteoporosis and osteolytic lesions.

A prospective study from Germany demonstrated a rapid and sustained reduction in pain, as well as long-term stabilization, using the balloon kyphoplasty technique.28 Recently, a retrospective study comparing kyphoplasty with radiation and systemic therapy showed that only after kyphoplasty was a standardized disability score decreased at 1 year follow-up. In addition, in that study, both kyphoplasty and radiation therapy were shown to have a statistically significant decrease in vertebral fracture rate compared with systemic therapy.28

The current patient had a left acetabular fracture as a result of the large solitary plasmacytoma in her pelvis. The patient underwent intralesional pelvic allograft fixation. This was accomplished with transsacral screws providing skeletal support for total hip arthroplasty. Accurate placement of the transsacral screws required a 2-approach technique. The patient was initially placed in the supine position for placement of percutaneous transsacral wires. Following successful wire placement, the patient was repositioned in the lateral position and underwent an iliofemoral approach for tumor debridement and graft sculpting, graft fixation, and total hip arthroplasty. The patient tolerated the procedure and was then transferred to the recovery room, where examination revealed excellent range of motion and full sensation.

Postoperative radiographs (Figure 2) and CT (Figure 3) confirmed curettage and cementation of the left iliac myelomatous lesion and optimal positioning of the cadaveric iliac graft, 2 fully threaded screws across the sacroiliotic joints, posterior column plate and screw fixation, and hybrid left total hip arthroplasty. Subsequent clinical and imaging follow-up revealed no evidence of local tumor recurrence or hardware failure to date. The patient continues to live symptom free of her plasmacytoma at 6-year follow-up.

Anteroposterior (A) and lateral (B) radiographs after curettage and cementation of the left iliac myelomatous lesion, cadaveric iliac graft, 2 fully threaded screws across the sacroiliac joints, posterior column plate and screw fixation, and hybrid left total hip arthroplasty.

Figure 2: Anteroposterior (A) and lateral (B) radiographs after curettage and cementation of the left iliac myelomatous lesion, cadaveric iliac graft, 2 fully threaded screws across the sacroiliac joints, posterior column plate and screw fixation, and hybrid left total hip arthroplasty.

Maximum intensity projection image (A) and axial (B), coronal (C), and sagittal (D) 2-dimensional computed tomography reconstructions of the pelvis after curettage and cementation of the left iliac myelomatous lesion (arrows), cadaveric iliac graft (asterisks), 2 fully threaded screws across the sacroiliac joints, posterior column plate and screw fixation, and hybrid left total hip arthroplasty.

Figure 3: Maximum intensity projection image (A) and axial (B), coronal (C), and sagittal (D) 2-dimensional computed tomography reconstructions of the pelvis after curettage and cementation of the left iliac myelomatous lesion (arrows), cadaveric iliac graft (asterisks), 2 fully threaded screws across the sacroiliac joints, posterior column plate and screw fixation, and hybrid left total hip arthroplasty.

References

  1. Hallek M, Bergsagel PL, Anderson KC. Multiple myeloma: increasing evidence for a multistep transformation process. Blood. 1998; 91(1):3–21.
  2. Landis SH, Murray T, Bolden S, et al. Cancer statistics. CA Cancer J Clin. 1998; 48(1):6–29. doi:10.3322/canjclin.48.1.6 [CrossRef]
  3. Durie BG. The role of anatomic and functional staging in myeloma: description of Durie/Salmon plus staging system. Eur J Cancer. 2006; 42(11):1539–1543. doi:10.1016/j.ejca.2005.11.037 [CrossRef]
  4. Selvanayagam P, Alexanian R. Plasma cell myeloma—new biological insights and advances in therapy. Blood. 1989; 73(4):865–879.
  5. Niesvizky R, Warrell RP Jr, . Pathophysiology and management of bone disease in multiple myeloma. Cancer Invest. 1997; 15(1):85–90. doi:10.3109/07357909709018921 [CrossRef]
  6. Buxbaum J. Mechanisms of disease: monoclonal immunoglobulin deposition. Amyloidosis, light chain deposition disease, and light and heavy chain deposition disease. Hematol Oncol Clin North Am. 1992; 6(2):323–346.
  7. Kyle RA, Gertz MA, Witzig TE, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc. 2003; 78(1):21–33. doi:10.4065/78.1.21 [CrossRef]
  8. Sawyer JR, Waldron JA, Jagannath S, et al. Cytogenetic findings in 200 patients with multiple myeloma. Cancer Genet Cytogenet. 1995; 82(1):41–49. doi:10.1016/0165-4608(94)00284-I [CrossRef]
  9. Fechtner K, Hillengass J, Delorme S, et al. Staging monoclonal plasma cell disease: comparison of the Durie-Salmon and the Durie-Salmon PLUS staging systems. Radiology. 2010; 257(1):195–204. doi:10.1148/radiol.10091809 [CrossRef]
  10. Dimopoulos MA, Kastritis E, Michalis E, et al. The International Scoring System (ISS) for multiple myeloma remains a robust prognostic tool independently of patients’ renal function. Ann Oncol. 2012; 23:722–729. doi:10.1093/annonc/mdr276 [CrossRef]
  11. Collins C. Multiple myeloma. In: Husband JE, Resnik RH, eds. Imaging of Oncology. 3rd ed. Essex, United Kingdom: Informa UK Ltd; 2010:851–869.
  12. Dinter DJ, Neff WK, Klaus J, et al. Comparison of whole-body MR imaging and conventional x-ray examination in patients with multiple myeloma and implications for therapy. Ann Hematol. 2009; 88(5):457–464. doi:10.1007/s00277-008-0621-6 [CrossRef]
  13. Mahnken AH, Wildberger JE, Gehbauer G, et al. Multidetector CT of the spine in multiple myeloma: comparison with MR imaging and radiography. AJR Am J Roentgenol. 2002; 178(6):1429–1436.
  14. Baur-Melnyk A, Buhmann S, Dürr HR, Reiser M. Role of MRI for the diagnosis and prognosis of multiple myeloma. Eur J Radiol. 2005; 55(1):56–63. doi:10.1016/j.ejrad.2005.01.017 [CrossRef]
  15. Horger M, Weisel K, Horger W, Mroue A, Fenchel M, Lichy M. Whole-body diffusion-weighted MRI with apparent diffusion coefficient mapping for early response monitoring in multiple myeloma: preliminary results. AJR Am J Roentgenol. 2011; 196(6):W790–W795. doi:10.2214/AJR.10.5979 [CrossRef]
  16. Sommer G, Klarhöfer M, Lenz C, Scheffler K, Bongartz G, Winter L. Signal characteristics of focal bone marrow lesions in patients with multiple myeloma using whole body T1w-TSE, T2w-STIR and diffusion-weighted imaging with background suppression. Eur Radiol. 2011; 21:857–862. doi:10.1007/s00330-010-1950-0 [CrossRef]
  17. Lütje S, de Rooy JW, Croockewit S. Role of radiography, MRI and FDG-PET/CT in diagnosing, staging and therapeutical evaluation of patients with multiple myeloma. Ann Hematol. 2009; 88(12):1161–1168. doi:10.1007/s00277-009-0829-0 [CrossRef]
  18. Shortt CP, Gleeson TG, Breen KA. Whole-body MRI versus PET in assessment of multiple myeloma disease activity. AJR Am J Roentgenol. 2009; 192(4):980–986. doi:10.2214/AJR.08.1633 [CrossRef]
  19. Sacchi S, Marcheselli R, Lazzaro A, et al. A randomized trial with melphalan and prednisone versus melphalan and prednisone plus thalidomide in newly diagnosed multiple myeloma patients not eligible for autologous stem cell transplant. Leuk Lymphoma. 2011; 52(10):1942–1948. doi:10.3109/10428194.2011.584006 [CrossRef]
  20. Richardson PG, Weller E, Lonial S, et al. Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood. 2010; 116(5):679–686. doi:10.1182/blood-2010-02-268862 [CrossRef]
  21. Ahn JS, Yang DH, Jung SH, et al. A comparison of bortezomib, cyclophosphamide, and dexamethasone (Vel-CD) chemotherapy without and with thalidomide (Vel-CTD) for the treatment of relapsed or refractory multiple myeloma. Ann Hematol. 2012; 91(7):1023–1030. doi:10.1007/s00277-012-1420-7 [CrossRef]
  22. Hutchison CA, Bradwell AR, Cook M. Treatment of acute renal failure secondary to multiple myeloma with chemotherapy and extended high cutoff hemodialysis. Clin J Am Soc Nephrol. 2009; 4(4):745–754. doi:10.2215/CJN.04590908 [CrossRef]
  23. Facon T, Mary JY, Pégourie B, et al. Dexamethasone-based regimens versus melphalanprednisone for elderly multiple myeloma patients ineligible for high-dose therapy. Blood. 2006; 107(4):1292–2198. doi:10.1182/blood-2005-04-1588 [CrossRef]
  24. Terpos E. Bisphosphonate anticancer activity in multiple myeloma. Anticancer Agents Med Chem. 2012; 12(2):129–136.
  25. Oken MM, Pomeroy C, Weisdorf D. Prophylactic antibiotics for the prevention of early infection in multiple myeloma. Am J Med. 1996; 100(6):624–628. doi:10.1016/S0002-9343(95)00043-7 [CrossRef]
  26. Chang SA, Lee SS, Ueng SW, Yuan LJ, Shih CH. Surgical treatment for pathological long bone fracture in patients with multiple myeloma: a retrospective analysis of 22 cases. Chang Gung Med J. 2001; 24(5):300–306.
  27. Hrabálek L, Bacovský J, Scudla V, Wamek T, Kalita O. Multiple spinal myeloma and its surgical management. Rozhl Chir. 2011; 90(5):270–276.
  28. Pflugmacher R, Schulz A, Schroeder RJ, Schaser KD, Klostermann CK, Melcher I. A prospective two-year follow-up of thoracic and lumbar osteolytic vertebral fractures caused by multiple myeloma treated with balloon kyphoplasty. Z Orthop Ihre Grenzgeb. 2007; 145(1):39–47. doi:10.1055/s-2007-960502 [CrossRef]

10.3928/01477447-20120822-01

Sign up to receive

Journal E-contents