title: Hip ontogenesis: how evolution, genes, and load history shape hip morphotype and cartilotype.
abstract: BACKGROUND
  Developmental hip disorders (DHDs), eg, developmental dysplasia of the hip, slipped capitis femoris epiphysis, and femoroacetabular impingement, can be considered morphology variants of the normal hip. The femoroacetabular morphology of DHD is believed to induce osteoarthritis (OA) through local cumulative mechanical overload acting on genetically controlled patterning systems and subsequent damage of joint structures. However, it is unclear why hip morphology differs between individuals with seemingly comparable load histories and why certain hips with DHD progress to symptomatic OA whereas others do not.
  
  
  OBJECTIVE
  We asked (1) which mechanical factors influence growth and development of the proximal femur; and (2) which genes or genetic mechanisms are associated with hip ontogenesis.
  
  
  METHODS
  We performed a systematic literature review of mechanical and genetic factors of hip ontogeny. We focused on three fields that in recent years have advanced our knowledge of adult hip morphology: imaging, evolution, and genetics.                                               WHERE ARE WE NOW?:                          Mechanical factors can be understood in view of human evolutionary peculiarities and may summate to load histories conducive to DHD. Genetic factors most likely act through multiple genes, each with modest effect sizes. Single genes that explain a DHD are therefore unlikely to be found. Apparently, the interplay between genes and load history not only determines hip morphotype, but also joint cartilage robustness ("cartilotype") and resistance to symptomatic OA.                                               WHERE DO WE NEED TO GO?:                          We need therapies that can improve both morphotype and cartilotype.                                               HOW DO WE GET THERE?:                          Better phenotyping, improving classification systems of hip morphology, and comparative population studies can be done with existing methods. Quantifying load histories likely requires new tools, but proof of principle of modifying morphotype in treatment of DDH and of cartilotype with exercise is available.
authors.affiliation: Orthopaedic Surgeon, Haga Hospital, The Hague, The Netherlands. thogervorst@gmail.com
authors.forename: Tom
authors.initials: T
authors.lastname: Hogervorst
authors.forename: Wouter
authors.initials: W
authors.lastname: Eilander
authors.forename: Joost T
authors.initials: JT
authors.lastname: Fikkers
authors.forename: Ingrid
authors.initials: I
authors.lastname: Meulenbelt
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D005075:Biological Evolution; D001696:Biomechanical Phenomena; D002358:Cartilage, Articular / Q000002:abnormalities* / Q000473:pathology / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D006621:Hip Joint / Q000002:abnormalities* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007592:Joint Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009024:Morphogenesis / Q000235:genetics; D009139:Musculoskeletal Abnormalities / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D015207:Osteoarthritis, Hip / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D010641:Phenotype; D012307:Risk Factors; D016474:Weight-Bearing; D055815:Young Adult