Abstract
We report here a case of multiple vertebral osteonecroses with intrasomatic gaseous dissection (Kümmell’s disease) occurring 1 year after the end of a 10-year course of denosumab treatment for osteoporosis without fractures. Histomorphometry and bone remodeling markers revealed major bone resorption and the persistence of an inhibition of bone formation. The presence of multiple empty lacunae in the bone provided evidence for high levels of osteocyte apoptosis. Osteocytes direct bone resorption (via the RANK/RANK-L/osteoprotegerin system) and formation (Wnt system, with SOST and DKK1) pathways. The vertebral osteonecrosis in our case may, therefore, have resulted from osteocyte apoptosis, decompensated by the sudden reactivation of bone remodeling after the cessation of denosumab treatment.
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References
Zhang X, Hamadeh IS, Song S et al (2016) Osteonecrosis of the jaw in the United States Food and Drug Administration’s Adverse Event Reporting System (FAERS). J Bone Miner Res 31:336–340
Popp AW, Zysset PK, Lippuner K (2016) Rebound-associated vertebral fractures after discontinuation of denosumab-from clinic and biomechanics. Osteoporos Int. https://doi.org/10.1007/s00198-015-3458-6
Anastasilakis AD, Makras P (2016) Multiple clinical vertebral fractures following denosumab discontinuation. Osteoporos Int 27:1929
Aubry-Rozier B, Gonzalez-Rodriguez E, Stoll D et al (2016) Severe spontaneous vertebral fractures after denosumab discontinuation: three case reports. Osteoporos Int 27:1923–1925
Polyzos SA, Terpos E (2016) Clinical vertebral fractures following denosumab discontinuation. Endocrine 27:1929–1930
Adami S, Idolazzi L, Fracassi E et al (2013) Osteoporosis treatment: when to discontinue and when to re-start. Bone Res 1:323–335
Libicher M, Appelt A, Berger I et al (2007) The intravertebral vacuum phenomenon as specific sign of osteonecrosis in vertebral compression fractures: results from a radiological and histological study. Eur Radiol 17:2248–2252
Lin CL, Lin RM, Huang KY et al (2013) MRI fluid sign is reliable in correlation with osteonecrosis after vertebral fractures: a histopathologic study. Eur Spine J 22:1617–1623
Feng SW, Chang MC, Wu HT et al (2011) Are intravertebral vacuum phenomena benign lesions? Eur Spine J 20:1341–1348
Papapoulos S, Lippuner K, Roux C et al (2015) The effect of 8 or 5 years of denosumab treatment in postmenopausal women with osteoporosis: results from the FREEDOM Extension study. Osteoporos Int 26:2773–2783
Weinstein RS (2012) Glucocorticoid-induced osteoporosis and osteonecrosis. Endocrinol Metab Clin N Am 41:595–611
Weinstein RS (2011) Clinical practice: glucocorticoid-induced bone disease. N Eng J Med 365:62–70
Manolagas SC, Parfitt AM (2013) For whom the bell tolls: distress signals from long-lived osteocytes and the pathogenesis of metabolic bone diseases. Bone 54:272–278
Rossini M, Gatti D, Adami S (2013) Involvement of Wnt/b-Catenin signalling in the treatment of osteoporosis. Calcif Tissue Int 93:121–132
Sims NA, Ng KW (2014) Implications of osteoblast-osteoclast interactions in the management of osteoporosis by antiresorptive agents denosumab and odanacatib. Curr Osteoporos Rep 12:98–106
Aghaloo TL, Cheong S, Bezouglaia O et al (2014) RANKL inhibitors induce osteonecrosis of the jaw in mice with periapical disease. J Bone Miner Res 29:843–854
de Oliveira CC, Brizeno LA, de Sousa FB et al (2016) Osteonecrosis of the jaw induced by receptor activator of nuclear factor-kappa B ligand (denosumab): review. Med Oral Patol Oral Cir Bucal 21:e431–e439
Bonewald LF (2011) The amazing osteocyte. J Bone Miner Res 2:229–238
Reid IR, Horne AM, Mihov B, Gamble GD (2017) Bone loss after denosumab: only partial protection with zoledronate. Calcif Tissue Int. https://doi.org/10.1007/s00223-017-0288-x
Leder BZ, Tsai JN, Uihlein AV et al (2015) Denosumab and teriparatide transitions in postmenopausal osteoporosis (the DATA-Switch study): extension of a randomised controlled trial. Lancet 386:1147–1155
Kim KM, Park W, Oh SY et al (2014) Distinctive role of 6-month teriparatide treatment on intractable bisphosphonate-related osteonecrosis of the jaw. Osteoporos Int 25:1625–1632
Acknowledgement
The authors would like to thank Pr Daniel Chappard, MD PD, Department of cellular and tissular pathology, University of Angers, France.
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Yves Maugars, Géraldine Bart, Pascale Guillot, Marguerite Chemel-Mary, Joëlle Glémarec, Mélanie Gahier-Penhoat, Benoit Le Goff, and Christelle Darrieutort-Laffite declare no conflict of interest.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Maugars, Y., Bart, G., Guillot, P. et al. Multiple Vertebral Osteonecroses (Kümmell’s Disease) After 10 Years on Denosumab: Is Osteocyte Apoptosis to Blame?. Calcif Tissue Int 102, 368–372 (2018). https://doi.org/10.1007/s00223-017-0357-1
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DOI: https://doi.org/10.1007/s00223-017-0357-1