Subscribe to RSS
DOI: 10.1055/a-1530-7882
Medikamentöse Therapie des primären Knochenmarködemsyndroms
Drug treatment of primary bone marrow edema syndromeZUSAMMENFASSUNG
Die medikamentöse Therapie des primären Knochenmarködemsyndroms (KMÖS) stellt einen wesentlichen Bestandteil des Gesamttherapiekonzeptes des KMÖS dar, wobei eine frühe Detektion und eine zeitnahe Initiierung von therapeutischen Maßnahmen von entscheidender Bedeutung ist. Zunächst gilt es, neben dem Ausschluss von sekundären Ursachen, mögliche Störungen der Kalziumhomöostase zu untersuchen und ggf. auszugleichen, da von einem maßgeblichen Einfluss dieser Faktoren in der Pathogenese des primären KMÖS ausgegangen wird. So stellen Mangelzustände, wie ein Vitamin-D-Mangel, eine häufige Ursache einer solchen Störung der Kalziumhomöostase dar und können konsekutiv zu einer enteralen Kalziumaufnahmestörung sowie zu einer Mineralisationsstörung des Knochens führen. Da ein KMÖS häufig mit einem systemischen respektive lokalen High-Turnover-Knochenstoffwechsel einhergeht, ist die Steuerung des Knochenstoffwechsels im Rahmen der Therapie besonders wichtig. Im Falle eines High-Turnover-Knochenstoffwechsels oder anderer klinischer Faktoren, wie einer gelenknahen subchondralen Lokalisation des Knochenmarködems mit Risiko einer Infraktion, einer schnellen Progredienz, einem großen Volumen oder ausgeprägten, immobilisierenden Schmerzen, kann eine antiresorptive Therapie im Off-Label-Verfahren in die Behandlung integriert werden. So konnte für den Einsatz von intravenösen Bisphosphonaten, wie Ibandronat oder Zoledronat, als auch des subkutan zu injizierenden Denosumab eine klinisch relevante Effektivität festgestellt werden, wobei bei Letzterem der schnellste Wirkeintritt zu erwarten ist. Zoledronat scheint, allerdings auf Kosten einer höheren Anzahl potenziell unerwünschter Ereignisse, das effektivste Wirkprofil zu besitzen. Einen alternativen Therapieansatz stellt der Off-Label-Einsatz des Prostazyklin-Analogons Iloprost dar, welches gemäß der Studienlage eine probate Therapieoption in frühen Stadien des Knochenmarködems darstellt, allerdings unter stationärer Überwachung zu applizieren ist. Parallel zur medikamentösen Therapie ist die chirurgische Mitbehandlung mit regelmäßiger Evaluation zur Anbohrung (Core Decompression) als Teil des Gesamttherapiekonzeptes zu eruieren.
SUMMARY
Drug treatment of primary bone marrow edema syndrome (BMES) represents an essential part of the therapy concept of BMES. An early detection and initiation of therapeutic intervention are of crucial importance. After the exclusion of secondary causes, possible disturbances of calcium homeostasis need to be investigated and, if necessary, balanced, as these factors likely have a decisive influence on the pathogenesis of primary BMES. Deficiencies, such as that of vitamin D, are a frequent cause of a disturbed calcium homeostasis and can potentially lead to impaired enteric calcium absorption and hypomineralization of the bone. Since BMES is often associated with systemic or local high-turnover bone metabolism, optimization of bone metabolism is of pivotal importance. In the case of high-turnover bone metabolism or clinical indications, such as a subchondral localization close to the joint with risk of secondary collapse, rapid progression, large volume, or pronounced immobilizing pain, off-label antiresorptive therapy can be integrated into the treatment. Intravenous bisphosphonates, such as ibandronate or zoledronate, as well as the monoclonal RANKL-antibody denosumab, have shown good efficacy and safety, with the latter being expected to have the most rapid onset of action. Zoledronate appears to have the most effective profile, but at the cost of a higher number of potential adverse events. An alternative therapeutic approach is the off-label use of the prostacyclin analogue iloprost, which, according to the literature, is an effective treatment option in early stages of BMES but must be administered under inpatient monitoring. Parallel to drug treatment, surgical co-treatment (e. g., core decompression) with regular evaluation need to be integrated into an optimized therapy concept.
Keywords
Bone marrow edema syndrome (BMES) - mineralization defect - vitamin D - antiresorptive treatmentPublication History
Article published online:
19 August 2021
© 2021. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
Literatur
- 1 Akhavan S, Martinkovich SC, Kasik C et al. Bone Marrow Edema, Clinical Significance, and Treatment Options:. A Review. J Am Acad Orthop Surg 2020; 28: e888-e899 DOI: 10.5435/JAAOS-D-20-00142.
- 2 Patel S. Primary bone marrow oedema syndromes. Rheumatology (Oxford) 2014; 53: 785-792 DOI: 10.1093/rheumatology/ket324.
- 3 Oehler N, Mussawy H, Schmidt T et al. Identification of vitamin D and other bone metabolism parameters as risk factors for primary bone marrow oedema syndrome. BMC Musculoskelet Disord 2018; 19: 451 DOI: 10.1186/s12891-018-2379-x.
- 4 Eriksen EF, Ringe JD. Bone marrow lesions: a universal bone response to injury?. Rheumatol Int 2012; 32: 575-584 DOI: 10.1007/s00296-011-2141-2.
- 5 Horas K, Fraissler L, Maier G et al. High Prevalence of Vitamin D Deficiency in Patients With Bone Marrow Edema Syndrome of the Foot and Ankle. Foot Ankle Int 2017; 38: 760-766 DOI: 10.1177/1071100717697427.
- 6 Sprinchorn AE, Sullivan R, Beischer AD. Transient bone marrow edema of the foot and ankle and its association with reduced systemic bone mineral density. Foot Ankle Int 2011; 32: S508-S512 DOI: 10.3113/FAI.2011.0508.
- 7 Berger CE, Kroner AH, Minai-Pour MB. et al Biochemical markers of bone metabolism in bone marrow edema syndrome of the hip. Bone 2003; 33: 346-351 DOI: 10.1016/s8756-3282(03)00164-9.
- 8 Pieropan S, Antoniazzi F, Tadiotto E. et al Bone Marrow Foot Oedema in Adolescents. The Role of Vitamin D. J Bone Metab 2019; 26: 241-246 DOI: 10.11005/jbm.2019.26.4.241.
- 9 Priemel M, von Domarus C, Klatte TO. et al Bone mineralization defects and vitamin D deficiency: histomorphometric analysis of iliac crest bone biopsies and circulating 25-hydroxyvitamin D in 675 patients. J Bone Miner Res 2010; 25: 305-312 DOI: 10.1359/jbmr.090728.
- 10 Busse B, Bale HA, Zimmermann EA. et al Vitamin D deficiency induces early signs of aging in human bone, increasing the risk of fracture. Sci Transl Med 2013; 5: 193-188 DOI: 10.1126/scitranslmed.3006286.
- 11 Schinke T, Schilling AF, Baranowsky A. et al Impaired gastric acidification negatively affects calcium homeostasis and bone mass. Nat Med 2009; 15: 674-681 DOI: 10.1038/nm.1963.
- 12 Alexandre C, Vico L. Pathophysiology of bone loss in disuse osteoporosis. Joint Bone Spine 2011; 78: 572-576 DOI: 10.1016/j.jbspin.2011.04.007.
- 13 Rumpler M, Wurger T, Roschger P. et al Microcracks and osteoclast resorption activity in vitro. Calcif Tissue Int 2012; 90: 230-238 DOI: 10.1007/s00223-011-9568-z.
- 14 Delsmann MM, Sturznickel J, Amling M. et al [Musculoskeletal laboratory diagnostics in competitive sport]. Orthopade 2021; DOI: 10.1007/s00132-021-04072-1.
- 15 Shuler FD, Wingate MK, Moore GH et al. Sports health benefits of vitamin d. Sports Health 2012; 4: 496-501 DOI: 10.1177/1941738112461621.
- 16 Chel V, Wijnhoven HA, Smit JH. et al Efficacy of different doses and time intervals of oral vitamin D supplementation with or without calcium in elderly nursing home residents. Osteoporos Int 2008; 19: 663-671 DOI: 10.1007/s00198-007-0465-2.
- 17 Dawson-Hughes B, Harris SS, Lichtenstein AH. et al Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet 2015; 115: 225-230 DOI: 10.1016/j.jand.2014.09.014.
- 18 Cormick G, Belizan JM. Calcium Intake and Health. Nutrients 2019; 11 DOI: 10.3390/nu11071606.
- 19 Simon MJ, Barvencik F, Luttke M. et al Intravenous bisphosphonates and vitamin D in the treatment of bone marrow oedema in professional athletes. Injury 2014; 45: 981-987 DOI: 10.1016/j.injury.2014.01.023.
- 20 Rolvien T, Schmidt T, Butscheidt S. et al Denosumab is effective in the treatment of bone marrow oedema syndrome. Injury 2017; 48: 874-879 DOI: 10.1016/j.injury.2017.02.020.
- 21 Vasikaran S, Eastell R, Bruyere O. et al Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporos Int 2011; 22: 391-420 DOI: 10.1007/s00198-010-1501-1.
- 22 Breer S, Oheim R, Krause M. et al Spontaneous osteonecrosis of the knee (SONK). Knee Surg Sports Traumatol Arthrosc 2013; 21: 340-345 DOI: 10.1007/s00167-012-2017-3.
- 23 Muller F, Appelt KA, Meier C. et al Zoledronic acid is more efficient than ibandronic acid in the treatment of symptomatic bone marrow lesions of the knee. Knee Surg Sports Traumatol Arthrosc 2020; 28: 408-417 DOI: 10.1007/s00167-019-05598-w.
- 24 Kim HK, Morgan-Bagley S, Kostenuik P. RANKL inhibition: a novel strategy to decrease femoral head deformity after ischemic osteonecrosis. J Bone Miner Res 2006; 21: 1946-1954 DOI: 10.1359/jbmr.060905.
- 25 Kim HK, Randall TS, Bian H. et al Ibandronate for prevention of femoral head deformity after ischemic necrosis of the capital femoral epiphysis in immature pigs. J Bone Joint Surg Am 2005; 87: 550-557 DOI: 10.2106/JBJS.D.02192.
- 26 Emad Y, Ragab Y, El-Shaarawy N. et al Transient osteoporosis of the hip, complete resolution after treatment with alendronate as observed by MRI description of eight cases and review of the literature. Clin Rheumatol 2012; 31: 1641-1647 DOI: 10.1007/s10067-012-2060-y.
- 27 Lai KA, Shen WJ, Yang CY. et al The use of alendronate to prevent early collapse of the femoral head in patients with nontraumatic osteonecrosis. A randomized clinical study. J Bone Joint Surg Am 2005; 87: 2155-2159 DOI: 10.2106/JBJS.D.02959.
- 28 Drake MT, Clarke BL, Khosla S. Bisphosphonates: mechanism of action and role in clinical practice. Mayo Clin Proc 2008; 83: 1032-1045 DOI: 10.4065/83.9.1032.
- 29 O’Connell NE, Wand BM, McAuley J. et al Interventions for treating pain and disability in adults with complex regional pain syndrome. Cochrane Database Syst Rev 2013; 10.1002/14651858.CD009416.pub2: CD009416 DOI: 10.1002/14651858.CD009416.pub2.
- 30 Brown JP, Dempster DW, Ding B. et al Bone remodeling in postmenopausal women who discontinued denosumab treatment: off-treatment biopsy study. J Bone Miner Res 2011; 26: 2737-2744 DOI: 10.1002/jbmr.448.
- 31 Bone HG, Wagman RB, Brandi ML. et al 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension. Lancet Diabetes Endocrinol 2017; 5: 513-523 DOI: 10.1016/S2213-8587(17)30138-9.
- 32 Cummings SR, San Martin J, McClung MR. et al Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 2009; 361: 756-765 DOI: 10.1056/NEJMoa0809493.
- 33 Zebaze RM, Libanati C, Austin M. et al Differing effects of denosumab and alendronate on cortical and trabecular bone. Bone 2014; 59: 173-179 DOI: 10.1016/j.bone.2013.11.016.
- 34 Tsourdi E, Langdahl B, Cohen-Solal M. et al Discontinuation of Denosumab therapy for osteoporosis: A systematic review and position statement by ECTS. Bone 2017; 105: 11-17 DOI: 10.1016/j.bone.2017.08.003.
- 35 Peterfy CG, Guermazi A, Zaim S. et al Whole-Organ Magnetic Resonance Imaging Score (WORMS) of the knee in osteoarthritis. Osteoarthritis Cartilage 2004; 12: 177-190 DOI: 10.1016/j.joca.2003.11.003.
- 36 Rolvien T, Schmidt T, Schmidt FN. et al Recovery of bone mineralization and quality during asfotase alfa treatment in an adult patient with infantile-onset hypophosphatasia. Bone 2019; 127: 67-74 DOI: 10.1016/j.bone.2019.05.036.
- 37 Classen T, Becker A, Landgraeber S. et al Long-term Clinical Results after Iloprost Treatment for Bone Marrow Edema and Avascular Necrosis. Orthop Rev (Pavia) 2016; 8: 6150 DOI: 10.4081/or.2016.6150.
- 38 Doury P. Bone-marrow oedema, transient osteoporosis, and algodystrophy. J Bone Joint Surg Br 1994; 76: 993-994
- 39 Grant SM, Goa KL. Iloprost A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in peripheral vascular disease, myocardial ischaemia and extracorporeal circulation procedures. Drugs 1992; 43: 889-924 DOI: 10.2165/00003495-199243060-00008.
- 40 Tosun HB, Uludag A, Demir S. et al Effectiveness of Iloprost in the Treatment of Bone Marrow Edema. Cureus 2020; 12: e10547 DOI: 10.7759/cureus.10547.
- 41 Aigner N, Petje G, Steinboeck G. et al Treatment of bone-marrow oedema of the talus with the prostacyclin analogue iloprost. An MRI-controlled investigation of a new method. J Bone Joint Surg Br 2001; 83: 855-858 DOI: 10.1302/0301-620x.83b6.11377.
- 42 Zippelius T, Hoff P, Strube P. et al Effects of iloprost on human mature osteoblasts in vitro. J Back Musculoskelet Rehabil 2019; 32: 897-903 DOI: 10.3233/BMR-171043.
- 43 Horterer H, Baumbach SF, Gregersen J. et al Treatment of Bone Marrow Edema of the Foot and Ankle With the Prostacyclin Analog Iloprost. Foot Ankle Int 2018; 39: 1183-1191 DOI: 10.1177/1071100718778557.
- 44 Pountos I, Giannoudis PV. The role of Iloprost on bone edema and osteonecrosis: Safety and clinical results. Expert Opin Drug Saf 2018; 17: 225-233 DOI: 10.1080/14740338.2018.1424828.
- 45 Baron R, Ferrari S, Russell RG. Denosumab and bisphosphonates: different mechanisms of action and effects. Bone 2011; 48: 677-692 DOI: 10.1016/j.bone.2010.11.020.
- 46 Weinstein RS, Roberson PK, Manolagas SC. Giant osteoclast formation and long-term oral bisphosphonate therapy. N Engl J Med 2009; 360: 53-62 DOI: 10.1056/NEJMoa0802633.
- 47 Kibbi L, Touma Z, Khoury N. et al Oral bisphosphonates in treatment of transient osteoporosis. Clin Rheumatol 2008; 27: 529-532 DOI: 10.1007/s10067-007-0766-z.
- 48 Singh D, Ferrero A, Rose B. et al Bone Marrow Edema Syndrome of the Foot and Ankle: Mid- to Long-Term Follow-up in 18 Patients. Foot Ankle Spec 2016; 9: 218-226 DOI: 10.1177/1938640015609986.
- 49 Kuchler L, Fehr T, Jeker R. Pain control with ibandronate for bone marrow oedema of the knee. Swiss Med Wkly 2020; 150: w20384 DOI: 10.4414/smw.2020.20384.
- 50 Ringe JD, Body JJ. A review of bone pain relief with ibandronate and other bisphosphonates in disorders of increased bone turnover. Clin Exp Rheumatol 2007; 25: 766-774
- 51 Bartl C, Imhoff A, Bartl R. Treatment of bone marrow edema syndrome with intravenous ibandronate. Arch Orthop Trauma Surg 2012; 132: 1781-1788 DOI: 10.1007/s00402-012-1617-1.
- 52 Flores-Robles BJ, Sanz-Sanz J, Sanabria-Sanchinel AA. et al Zoledronic Acid Treatment in Primary Bone Marrow Edema Syndrome. J Pain Palliat Care Pharmacother 2017; 31: 52-56 DOI: 10.1080/15360288.2016.1276993.
- 53 Seok H, Kim YT, Kim SH. et al Treatment of transient osteoporosis of the hip with intravenous zoledronate a case report. Ann Rehabil Med 2011; 35: 432-435 DOI: 10.5535/arm.2011.35.3.432.
- 54 Vasiliadis AV, Zidrou C, Charitoudis G. et al Single-Dose Therapy of Zoledronic Acid for the Treatment of Primary Bone Marrow Edema Syndrome. Cureus 2021; 13: e13977 DOI: 10.7759/cureus.13977.
- 55 Evangelatos G, Fragoulis GE, Iliopoulos A. Zoledronic acid in nine patients with transient osteoporosis of the hip. Clin Rheumatol 2020; 39: 291-293 DOI: 10.1007/s10067-019-04840-7.
- 56 Agarwala S, Vijayvargiya M. Single Dose Therapy of Zoledronic Acid for the Treatment of Transient Osteoporosis of Hip. Ann Rehabil Med 2019; 43: 314-320 DOI: 10.5535/arm.2019.43.3.314.
- 57 Geith T, Mutschler W, Berger F. [Therapy of bone marrow edema syndrome in the knee with denosumab. Case report]. Unfallchirurg 2015; 118: 230-232 DOI: 10.1007/s00113-014-2692-2.
- 58 Fabbriciani G, Pirro M, Manfredelli MR. et al Transient osteoporosis of the hip: successful treatment with teriparatide. Rheumatol Int 2012; 32: 1367-1370 DOI: 10.1007/s00296-010-1404-7.
- 59 Horikawa A, Miyakoshi N, Hongo M. et al Treatment of spontaneous osteonecrosis of the knee by daily teriparatide: A report of 3 cases. Medicine (Baltimore) 2020; 99: e18989 DOI: 10.1097/MD.0000000000018989.