Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2012

Open Access 01-06-2012 | Proceedings

Pathophysiology and medical treatment of pain in fibrous dysplasia of bone

Authors: Roland D Chapurlat, Deborah Gensburger, Juan M Jimenez-Andrade, Joseph R Ghilardi, Marilyn Kelly, Patrick Mantyh

Published in: Orphanet Journal of Rare Diseases | Special Issue 1/2012

Login to get access

Abstract

One of the most common complications of fibrous dysplasia of bone (FD) is bone pain. Usual pain killers are often of inadequate efficacy to control this bone pain. The mechanism of bone pain in FD remains uncertain, but by analogy with bone tumors one may consider that ectopic sprouting and formation of neuroma-like structures by sensory and sympathetic nerve fibers also occur in the dysplastic skeleton. Bone pain has been reported in up to 81% of adults and 49% of children. It affects predominantly the lower limbs and the spine. The degree of pain is highly variable and adults reports more pain than children. Bisphosphonates have been shown to reduce bone pain in uncontrolled studies. Their influence on bone strength remains unknown. In a randomized trial testing alendronate, bone pain was not significantly improved. Another trial assessing the effect of risedronate is ongoing. Possible future therapies include tocilizumab, denosumab and drugs targeting nerve growth factor and its receptor TrkA.
Literature
1.
Firat D, Stutzman L: Fibrous dysplasia of the bone. Review of twenty-four cases. Am J Med. 1968, 44: 421-429. 10.1016/0002-9343(68)90112-5.CrossRefPubMed
2.
Chapurlat RD, Delmas PD, Liens D, Meunier PJ: Long-term effects of intravenous pamidronate in fibrous dysplasia of bone. J Bone Miner Res. 1997, 12 (10): 1746-52. 10.1359/jbmr.1997.12.10.1746.CrossRefPubMed
3.
Kelly MH, Brillante B, Collins MT: Pain in fibrous dysplasia of bone: age-related changes and the anatomical distribution of skeletal lesions. Osteoporos Int. 2008, 19: 57-63. 10.1007/s00198-007-0425-x.CrossRefPubMed
4.
Kelly MH, Brillante B, Kushner H, Gehron Robey P, Collins MT: Physical function is impaired but quality of life preserved in patients with fibrous dysplasia of bone. Bone. 2005, 37: 388-394. 10.1016/j.bone.2005.04.026.CrossRefPubMed
5.
Liens D, Delmas PD, Meunier PJ: Long-term effects of intravenous pamidronate in fibrous dysplasia of bone. Lancet. 1994, 343 (8903): 953-4. 10.1016/S0140-6736(94)90069-8.CrossRefPubMed
6.
Jimenez-Andrade JM, Mantyh WG, Bloom AP, Freeman KT, Ghilardi JR, Kuskowski MA, Mantyh PW: The effect of aging on the density of the sensory nerve fiber innervation of bone and acute skeletal pain. Neurobiol Aging. 2010, 33: 921-932.PubMedCentralCrossRefPubMed
7.
Jimenez-Andrade JM, Mantyh WG, Bloom AP, Xu H, Ferng AS, Dussor G, Vanderah TW, Mantyh PW: A phenotypically restricted set of primary afferent nerve fibers innervate the bone versus skin: Therapeutic opportunity for treating skeletal pain. Bone. 2011, 46: 523-529. 10.1016/j.bone.2009.09.013.
8.
Zylka MJ, Rice FL, Anderson DJ: Topographically distinct epidermal nociceptive circuits revealed by axonal tracers targeted to Mrgprd. Neuron. 2005, 45: 17-25. 10.1016/j.neuron.2004.12.015.CrossRefPubMed
9.
Mantyh PW: Cancer pain and its impact on diagnosis, survival and quality of life. Nat Rev Neurosci. 2006, 7: 797-809.CrossRefPubMed
10.
Lane NE, Schnitzer TJ, Birbara CA, Mokhtarani M, Shelton DL, Smith MD, Brown MT: Tanezumab for the treatment of pain from osteoarthritis of the knee. N Engl J Med. 2010, 363: 1521-1531. 10.1056/NEJMoa0901510.CrossRefPubMed
11.
Mantyh WG, Jimenez-Andrade JM, Stake JI, Bloom AP, Kaczmarska MJ, Taylor RN, Freeman KT, Ghilardi JR, Kuskowski MA, Mantyh PW: Blockade of nerve sprouting and neuroma formation markedly attenuates the development of late stage cancer pain. Neuroscience. 2010, 171: 588-598. 10.1016/j.neuroscience.2010.08.056.PubMedCentralCrossRefPubMed
12.
Halvorson KG, Kubota K, Sevcik MA, Lindsay TH, Sotillo JE, Ghilardi JR, Rosol TJ, Boustany L, Shelton DL, Mantyh PW: A blocking antibody to nerve growth factor attenuates skeletal pain induced by prostate tumor cells growing in bone. Cancer Res. 2005, 65: 9426-9435. 10.1158/0008-5472.CAN-05-0826.CrossRefPubMed
13.
Jimenez-Andrade JM, Bloom AP, Stake JI, Mantyh WG, Taylor RN, Freeman KT, Ghilardi JR, Kuskowski MA, Mantyh PW: Pathological sprouting of adult nociceptors in chronic prostate cancer-induced bone pain. J Neurosci. 2010, 30: 14649-14656. 10.1523/JNEUROSCI.3300-10.2010.PubMedCentralCrossRefPubMed
14.
Skaper SD, Pollock M, Facci L: Mast cells differentially express and release active high molecular weight neurotrophins. Brain Res Mol Brain Res. 2001, 97: 177-185.CrossRefPubMed
15.
Ehrhard PB, Erb P, Graumann U, Otten U: Expression of nerve growth factor and nerve growth factor receptor tyrosine kinase Trk in activated CD4-positive T-cell clones. Proc Natl Acad Sci USA. 1993, 90: 10984-10988. 10.1073/pnas.90.23.10984.PubMedCentralCrossRefPubMed
16.
Freemont AJ, Watkins A, Le Maitre C, Baird P, Jeziorska M, Knight MT, Ross ER, O'Brien JP, Hoyland JA: Nerve growth factor expression and innervation of the painful intervertebral disc. J Pathol. 2002, 197: 286-292. 10.1002/path.1108.CrossRefPubMed
17.
Ashraf S, Wibberley H, Mapp PI, Hill R, Wilson D, Walsh DA: Increased vascular penetration and nerve growth in the meniscus: a potential source of pain in osteoarthritis. Ann Rheum Dis. 2011, 70: 523-529. 10.1136/ard.2010.137844.CrossRefPubMed
18.
Suri S, Gill SE, Massena de Camin S, Wilson D, McWilliams DF, Walsh DA: Neurovascular invasion at the osteochondral junction and in osteophytes in osteoarthritis. Ann Rheum Dis. 2007, 66: 1423-1428. 10.1136/ard.2006.063354.PubMedCentralCrossRefPubMed
19.
Wu Z, Nagata K, Iijima T: Involvement of sensory nerves and immune cells in osteophyte formation in the ankle joint of adjuvant arthritic rats. Histochem Cell Biol. 2002, 118: 213-220.PubMed
20.
Collins MT, Kushner H, Reynolds JC, Chebli C, Kelly MH, Gupta A, et al: An instrument to measure skeletal burden and predict functional outcome in fibrous dysplasia of bone. J Bone Miner Res. 2005, 20 (2): 219-226.CrossRefPubMed
21.
Daut RL, Cleeland CS, Flanery RC: Development of the Wisconsin Brief Pain Questionnaire to assess pain in cancer and other diseases. Pain. 1983, 17 (2): 197-210. 10.1016/0304-3959(83)90143-4.CrossRefPubMed
22.
Chapurlat RD, Hugueny P, Delmas PD, Meunier PJ: Treatment of fibrous dysplasia of bone with intravenous pamidronate: long-term effectiveness and evaluation of predictors of response to treatment. Bone. 2004, 35 (1): 235-42. 10.1016/j.bone.2004.03.004.CrossRefPubMed
23.
Chapurlat R, Meunier PJ: The nonsurgical treatment of fibrous dysplasia. Rev Rhum Engl Ed. 1999, 66 (1): 1-3.PubMed
24.
Parisi MS, Oliveri B, Mautalen CA: Effect of intravenous pamidronate on bone markers and local bone mineral density in fibrous dysplasia. Bone. 2003, 33 (4): 582-8. 10.1016/S8756-3282(03)00221-7.CrossRefPubMed
25.
Weinstein RS: Long-term aminobisphosphonate treatment of fibrous dysplasia: spectacular increase in bone density. J Bone Miner Res. 1997, 12 (8): 1314-5. 10.1359/jbmr.1997.12.8.1314.CrossRefPubMed
26.
Kitagawa Y, Tamai K, Ito H: Oral alendronate treatment for polyostotic fibrous dysplasia: a case report. J Orthop Sci. 2004, 9 (5): 521-5.CrossRefPubMed
27.
Lane JM, Khan SN, O'Connor WJ, Nydick M, Hommen JP, Schneider R, Tomin E, Brand J, Curtin J: Bisphosphonate therapy in fibrous dysplasia. Clin Orthop Relat Res. 2001, 382: 6-12.CrossRefPubMed
28.
Chapurlat RD: Medical therapy in adults with fibrous dysplasia of bone. J Bone Miner Res. 2006, 21 (Suppl 2): P114-9.CrossRefPubMed
29.
Plotkin H, Rauch F, Zeitlin L, Munns C, Travers R, Glorieux FH: Effect of pamidronate treatment in children with polyostotic fibrous dysplasia of bone. J Clin Endocrinol Metab. 2003, 88 (10): 4569-75. 10.1210/jc.2003-030050.CrossRefPubMed
30.
Lala R, Matarazzo P, Bertelloni S, Buzi F, Rigon F, de Sanctis C: Pamidronate treatment of bone fibrous dysplasia in nine children with McCune-Albright syndrome. Acta Paediatr. 2000, 89 (2): 188-93. 10.1111/j.1651-2227.2000.tb01214.x.CrossRefPubMed
31.
Isaia GC, Lala R, Defilippi C, Matarazzo P, Andreo M, Roggia C, Priolo G, de Sanctis C: Bone turnover in children and adolescents with McCune-Albright syndrome treated with pamidronate for bone fibrous dysplasia. Calcif Tissue Int. 2002, 71 (2): 121-8. 10.1007/s00223-001-1098-7.CrossRefPubMed
32.
Zacharin M, O’Sullivan M: Intravenous pamidronate treatment of polyostotic fibrous dysplasia associated with the McCune-Albright syndrome. J Pediatr. 2000, 137 (3): 403-9. 10.1067/mpd.2000.107836.CrossRefPubMed
33.
Kuznetsov SA, Cherman N, Riminucci M, Collins MT, Gehron Robey P, Bianco P: Age-dependent demise of GNAS-mutated skeletal stem cells and “normalization” of fibrous dysplasia of bone. J Bone Miner Res. 2008, 23 (11): 1741-40. 10.1359/jbmr.080704.CrossRef
34.
35.
36.
Yamamoto T, Ozono K, Kasayama S, Yoh K, Hiroshima K, Takagi M, Matsumoto S, Michigami T, Yamaoka K, Kishimoto T, Okada S: Increased IL-6 production by cells isolated from the fibrous bone dysplasia tissues in patients with McCune-Albright syndrome. J Clin Invest. 1996, 98: 30-5. 10.1172/JCI118773.PubMedCentralCrossRefPubMed
37.
Riminucci M, Kuznetsov SA, Cherman N, Corsi A, Bianco P, Gehron Robey P: Osteoclastogenesis in fibrous dysplasia of bone : in situ and in vitro analysis of IL-6 expression. Bone. 2003, 33: 434-42. 10.1016/S8756-3282(03)00064-4.CrossRefPubMed
38.
Garnero P, Mareau E, Thompson E, Woodworth T, Smolen J: Rapid and sustained improvement in bone and cartilage markers with the interleukin-6 receptor inhibitor tocilizumab plus methotrexate in rheumatoid arthritis patients with an inadequate response to methotrexate. Arthritis Rheum. 2010, 62: 33-43. 10.1002/art.25053.CrossRefPubMed
Metadata
Title
Pathophysiology and medical treatment of pain in fibrous dysplasia of bone
Authors
Roland D Chapurlat
Deborah Gensburger
Juan M Jimenez-Andrade
Joseph R Ghilardi
Marilyn Kelly
Patrick Mantyh
Publication date
01-06-2012
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue Special Issue 1/2012
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/1750-1172-7-S1-S3

Other articles of this Special Issue 1/2012

Orphanet Journal of Rare Diseases 1/2012 Go to the issue

Proceedings

Clinical guidelines for the management of craniofacial fibrous dysplasia

Proceedings

The role of SH3BP2 in the pathophysiology of cherubism

Proceedings

McCune-Albright syndrome and the extraskeletal manifestations of fibrous dysplasia

Proceedings

Cherubism: best clinical practice

Proceedings

The surgical management of fibrous dysplasia of bone