Priority 7 from the Rare Musculoskeletal Diseases in Adulthood PSP

UNCERTAINTY: What are the benefits and side effects of drug treatment for people with rare metabolic bone disorders in the short and long term? What is the optimal length of treatment? (JLA PSP Priority 7)
Overall ranking 7
JLA question ID 0076/7
Explanatory note Not available for this PSP

XLH has generally been treated with an activated vitamin D metabolite (calcitriol or alfacalciol) and phosphate supplements, but their effectiveness is limited. A recent randomised controlled trial demonstrates that use of the anti-FGF23 monoclonal antibody (KRN23; Burosumab) reverses biochemical  abnormalities in XLH, increasing serum phosphate and 1,25(OH)2D. concentrations (Imel EA et al,J Clin Endocrinol Metab 2015; 100: 2565-2573). Phase III clinical trials of Burosumab are underway and NICE are conducting a Highly Specialised Technologies Evaluation of Burosumab, which is due to be published in October 2018. 

A randomized, double blind, placebo-controlled trial of alendronate treatment for fibrous dysplasia of bone. Boyce AM1, Kelly MH, Brillante BA, Kushner H, Wientroub S, Riminucci M, Bianco P, Robey PG, Collins MT. J Clin Endocrinol Metab. 2014 Nov;99(11):4133-40. (n=24 adults)

Outcome of Long-Term Bisphosphonate Therapy in McCune-Albright Syndrome and Polyostotic Fibrous Dysplasia. Majoor BC1,2, Appelman-Dijkstra NM1,3, Fiocco M4,5, van de Sande MA1,2, Dijkstra PS1,2, Hamdy NA1,3. J Bone Miner Res. 2017 Feb;32(2):264-276. (n=41)

Pegvisomant for the treatment of gsp-mediated growth hormone excess in patients with McCune-Albright syndrome. Akintoye SO1, Kelly MH, Brillante B, Cherman N, Turner S, Butman JA, Robey PG, Collins MT. J Clin Endocrinol Metab. 2006 Aug;91(8):2960-6. (n=5)

Bisphosphonate treatment of bone fibrous dysplasia in McCune-Albright syndrome. Lala R1, Matarazzo P, Andreo M, Marzari D, Bellone J, Corrias A, de Sanctis C; Study Group for Gs alpha Protein Related Diseases of the Italian Society for Pediatric Endocrinology and Diabetes. Pediatr Endocrinol Metab. 2006 May;19 Suppl 2:583-93. (n=14 5-18.7yr)

Pamidronate treatment in bone fibrous dysplasia in children and adolescents with McCune-Albright syndrome. Matarazzo P1, Lala R, Masi G, Andreo M, Altare F, de Sanctis C. J Pediatr Endocrinol Metab. 2002;15 Suppl 3:929-37.

Long-term effects of intravenous pamidronate in fibrous dysplasia of bone. Chapurlat RD1, Delmas PD, Liens D, Meunier PJ. J Bone Miner Res. 1997 Oct;12(10):1746-52. (n=20)  

Health Research Classification System category Musculoskeletal
Extra information provided by this PSP
Original uncertainty examples Does denosumab differ from BPs? And why? Impact for long-term therapy? ~ Have there been changes seen with those who took medical trials as children? ~ What evidence is there so far into the long term benefit of bisphosphonates given in childhood? ~ What are the long term effects of treatment? My niece is 10 and receives biphosponate treatment. What are the long term effects if she continues? Can it ultimately cause more harm than good? Is it really helping? ~ What is the long term effect on taking the current drugs for xlh and ADHR and do they help prevent osteomalacia, fractures/ breaks later in life? 
Submitted by Individual survey submissions categorised by Health or Social Care Professionals, Organisations representing people with rare musculoskeletal diseases, people with rare musculoskeletal diseases, relatives/carers/friends, Other.  For full details of the type of submitter for each individual question, please see the spreadsheet of data held on the JLA website. ~ What is the long term effect on taking the current drugs for xlh and ADHR and do they help prevent osteomalacia, fractures/ breaks later in life? 
PSP information
PSP unique ID 0076
PSP name Rare Musculoskeletal Diseases in Adulthood
Total number of uncertainties identified by this PSP. 39  (To see a full list of all uncertainties identified, please see the detailed spreadsheet held on the JLA website)
Date of priority setting workshop 18 June 2018