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. 2023 Jun 6;18(1):139.
doi: 10.1186/s13023-023-02738-x.

Achondroplasia natural history study (CLARITY): 60-year experience in orthopedic surgery from four skeletal dysplasia centers

Nickolas J Nahm  1 , W G Stuart Mackenzie  2 , William G Mackenzie  2 , Ethan Gough  3 , S Shahrukh Hashmi  4 , Jacqueline T Hecht  4 , Janet M Legare  5 , Mary Ellen Little  2 , Peggy Modaff  5 , Richard M Pauli  5 , David F Rodriguez-Buritica  4 , Maria Elena Serna  4 , Cory J Smid  5 , Julie Hoover-Fong  6 , Michael B Bober  7
Affiliations

Achondroplasia natural history study (CLARITY): 60-year experience in orthopedic surgery from four skeletal dysplasia centers

Nickolas J Nahm et al. Orphanet J Rare Dis. .

Abstract

Background: The purpose of this study was to describe the frequency and risk factors for orthopedic surgery in patients with achondroplasia. CLARITY (The Achondroplasia Natural History Study) includes clinical data from achondroplasia patients receiving treatment at four skeletal dysplasia centers in the United States from 1957 to 2018. Data were entered and stored in a Research Electronic Data Capture (REDCap) database.

Results: Information from one thousand three hundred and seventy-four patients with achondroplasia were included in this study. Four hundred and eight (29.7%) patients had at least one orthopedic surgery during their lifetime and 299 (21.8%) patients underwent multiple procedures. 12.7% (n = 175) of patients underwent spine surgery at a mean age at first surgery of 22.4 ± 15.3 years old. The median age was 16.7 years old (0.1-67.4). 21.2% (n = 291) of patients underwent lower extremity surgery at a mean age at first surgery of 9.9 ± 8.3 years old with a median age of 8.2 years (0.2-57.8). The most common spinal procedure was decompression (152 patients underwent 271 laminectomy procedures), while the most common lower extremity procedure was osteotomy (200 patients underwent 434 procedures). Fifty-eight (4.2%) patients had both a spine and lower extremity surgery. Specific risk factors increasing the likelihood of orthopedic surgery included: patients with hydrocephalus requiring shunt placement having higher odds of undergoing spine surgery (OR 1.97, 95% CI 1.14-3.26); patients having a cervicomedullary decompression also had higher odds of undergoing spine surgery (OR 1.85, 95% CI 1.30-2.63); and having lower extremity surgery increased the odds of spine surgery (OR 2.05, 95% CI 1.45-2.90).

Conclusions: Orthopedic surgery was a common occurrence in achondroplasia with 29.7% of patients undergoing at least one orthopedic procedure. Spine surgery (12.7%) was less common and occurred at a later age than lower extremity surgery (21.2%). Cervicomedullary decompression and hydrocephalus with shunt placement were associated with an increased risk for spine surgery. The results from CLARITY, the largest natural history study of achondroplasia, should aid clinicians in counseling patients and families about orthopedic surgery.

Keywords: Achondroplasia; Genu varum; Spinal stenosis; Thoracolumbar kyphosis.

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Conflict of interest statement

This is an investigator-initiated independent research study supported, in part, by BioMarin, Inc. The data presented in this paper do not pertain to the investigational pharmaceuticals under development by BioMarin, Ascendis, Therachon, or QED. These following competing activities were reviewed and approved by our institutions. J.E.H.-F. has participated in Advisory Boards sponsored by BioMarin pertaining to achondroplasia. J.E.H.-F. has been consulted by BioMarin, Alexion, Therachon/Pfizer, QED, Innoskel and NovoNordisk for clinical issues related to achondroplasia and other genetic skeletal conditions and acts as a site principal investigator (PI) for clinical trials for BioMarin, Therachon/Pfizer and QED. M.B.B. has participated in Advisory Boards sponsored by BioMarin, consulted with BioMarin, Ascendis, Therachon/Pfizer, and QED for clinical issues related achondroplasia as well as acting as a site PI in their clinical trials. He is a member of Alexion’s Speaker’s Bureau (HPP). M.B.B. is a site PI and consultant for MedLife Discoveries (RCDP) and Ultragenyx. He is a site PI for Shire (Hunter). J.T.H. has participated in Advisory Boards pertaining to achondroplasia sponsored by BioMarin. D.R.-B. has participated in Advisory Boards pertaining to achondroplasia sponsored by BioMarin and has lectured for BioMarin. J.L. is a site PI for Ascendis and is a paid speaker for BioMarin. The other authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Kaplan Meier curve of patients undergoing any orthopaedic, lower extremity or spine surgery by age. These data represent cumulative probability of a surgery (y-axis) as a function of age (x-axis). At 10 years of age, 19.0% of patients had an orthopaedic procedure with 16.2% having a lower extremity surgery and 3.4% with spine surgery. At 20 years of age, 41.8% of patients had an orthopaedic procedure with 32.0% having a lower extremity surgery and 14.4% with spine surgery. At 40 years of age, 60.9% had an orthopaedic procedure with 35.3% having a lower extremity surgery and 39.6% with spine surgery. At 60 years of age, 85.3% had an orthopaedic procedure with 52.6% having lower extremity surgery and 68.9% with spine surgery. At 80 years of age, 95.1% had an orthopaedic procedure with 52.6% having lower extremity surgery and 89.6% with spine surgery
Fig. 2
Fig. 2
Kaplan Meier curve of patients undergoing laminectomies and spinal fusions by age. These data represent cumulative probability of a surgery (y-axis) as a function of age (x-axis). At 10 years of age, 3.4% of patients had a laminectomy and 2.4% had a fusion surgery. At 20 years of age, 14.8% of patients had a laminectomy and 10.5% had a fusion surgery. At 40 years of age, 40.9% had a laminectomy and 24.1% had fusion surgery. At 60 years of age, 69.1% had a laminectomy and 39.9% had a fusion. At 80 years of age, 93.4% had a laminectomy with 55.0% had fusion surgery
Fig. 3
Fig. 3
Indications for first time spine surgery. A Venn diagram is used to show the most common indications and their overlap for spine surgery. The most common indications were symptomatic spinal stenosis followed by thoracolumbar kyphosis. Additional, less frequent indications are not represented (n = 37)
Fig. 4
Fig. 4
Indications for repeat spine surgery. A Venn diagram is used to show the most common indications and their overlap for repeat spine surgery. The most common indications were spinal stenosis followed by thoracolumbar kyphosis. Additional, less frequent indications are not represented (n = 72)
Fig. 5
Fig. 5
Indications for first time lower extremity surgery. A Venn diagram is used to show the most common indications and their overlap for lower extremity surgery. The most common indications were malalignment followed by pain. Additional, less frequent indications are not represented (n = 37)
Fig. 6
Fig. 6
Indications for repeat lower extremity surgery. A Venn diagram is used to show the most common indications and their overlap for repeat lower extremity surgery. The most common indications were malalignment followed by pain. Additional, less frequent indications are not represented (n = 81)
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