Int J Clin Pediatr

International Journal of Clinical Pediatrics, ISSN 1927-1255 print, 1927-1263 online, Open Access

Article copyright, the authors; Journal compilation copyright, Int J Clin Pediatr and Elmer Press Inc

Journal website https://ijcp.elmerpub.com

Review

Volume 000, Number 000, May 2026, pages 000-000

Associated Arthropathies in Pediatric Endocrine Disorders: A Systematic Review and Narrative Synthesis

↓ Figure 1. PRISMA-style study-selection pathway for the systematic review. This PRISMA-style figure summarizes database searching, duplicate removal, screening, full-text eligibility assessment, and final inclusion of 15 studies in the qualitative synthesis.

↓ Figure 2. Arthropathy in pediatric endocrine disorders: clinical patterns, diagnostic clues, and management pathways. Infographic summarizing disorder-specific joint manifestations, diagnostic red flags, and management considerations in pediatric endocrine arthropathy. SCFE: slipped capital femoral epiphysis.

↓ **Table 1.** Study Characteristics and Key Clinical Messages of Arthropathy in Pediatric Endocrine Disorders
Study (first author, year)	Study type	Population (endocrine disorder)	Key findings related to arthropathy
GH: growth hormone; LJM: limited joint mobility; SCFE: slipped capital femoral epiphysis; UK: United Kingdom; USA: United States of America.
Rosenbloom, 2013 [9]	Historical cohort analysis (1970s vs. 1990s)	476 children with type 1 diabetes (USA)	Prevalence of limited joint mobility (LJM) declined from ∼30% to ∼7% over two decades; LJM associated with poor metabolic control and ∼4-fold increased risk of microvascular complications.
Clarke, 1990 [11]	Cross-sectional	70 children with type 1 diabetes (UK)	LJM prevalence 31% by prayer sign; 7% using strict criteria. More frequent with older age and longer diabetes duration; no significant HbA1c correlation in this small cohort.
Montana, 1995 [12]	Cross-sectional	89 adolescents with type 1 diabetes (Spain)	LJM present in ∼42%; moderate–severe in 14%. Strong association with microalbuminuria, suggesting linkage with early diabetic microangiopathy.
Arkkila, 2003 [13]	Narrative review (pediatric data included)	Children and adults with diabetes mellitus	Summarized musculoskeletal complications of diabetes, including LJM and cheiroarthropathy; highlighted higher prevalence with longer disease duration and poor glycemic control.
McLean, 1995 [4]	Literature review and case series	Pediatric and adult hypothyroid patients	Hypothyroidism is associated with arthralgia, non-inflammatory joint effusions, and in children, epiphyseal dysgenesis and SCFE; synovial fluid typically viscous and acellular.
Gutch, 2013 [14]	Prospective cohort (6-month follow-up)	29 children with juvenile hypothyroidism (India)	Delayed bone age and metaphyseal thickening in all patients; short stature improved with therapy, but epiphyseal abnormalities persisted in >50% after 6 months; one SCFE case identified.
Lehmann 2006 [15]	Retrospective cohort	85 children with SCFE and endocrine disorders (USA)	Endocrine-related SCFE frequently bilateral and atypical; hypothyroidism and GH deficiency most common associations; recommended routine endocrine screening in atypical SCFE.
Karthikeyan, 2012 [16]	Case report	8-year-old girl with pseudohypoparathyroidism type 1b (UK)	Bilateral SCFE as presenting feature; associated with physeal widening and genu valgum; orthopedic fixation plus calcitriol led to physeal healing over 2 years.
Lindgren, 2023 [17]	Review with case series	90 patients with acromegaly (mostly adults; adolescents included, but pediatric subgroup not separately reported)	Highlighted endocrine etiologies (hypothyroidism, GH deficiency, hyperparathyroidism); endocrine-related SCFE occurred outside typical age/weight range and was frequently bilateral.
Dons, 1988 [18]	Retrospective cohort (long-term follow-up)	31 patients with long-term controlled acromegaly (mixed-age cohort; pediatric subgroup not separately reported)	Universal radiographic osteoarthritis at baseline; continued progression of hand and spine arthropathy despite biochemical remission in >80%; findings derive from a mixed-age cohort rather than a pediatric-only series.
Pelsma, 2021 [19]	Prospective cohort (9-year follow-up)	1 adolescent with Graves disease (Brazil)	Universal radiographic osteoarthritis at baseline; continued progression of hand and spine arthropathy despite biochemical remission in >80%.
Perini, 2019 [20]	Case report	16-year-old boy with Graves disease (Brazil)	Thyroid acropachy developed 2 years after radioiodine therapy; periosteal new bone formation and digital clubbing; rare pediatric manifestation.
Benina, 2023 [21]	Case series	Three children with primary hyperparathyroidism (Korea)	Presentations included bone pain, gait disturbance, and fractures; all due to parathyroid adenoma; musculoskeletal symptoms improved after surgery.
Lodish, 2018 [22]	Retrospective cohort	Children with endogenous Cushing syndrome (USA)	Vertebral fractures and musculoskeletal pain are common at diagnosis; bone density improved after cure, but some skeletal morbidity persisted.

↓ Table 1. Study Characteristics and Key Clinical Messages of Arthropathy in Pediatric Endocrine Disorders

Study (first author, year)

Study type

Population (endocrine disorder)

Key findings related to arthropathy

GH: growth hormone; LJM: limited joint mobility; SCFE: slipped capital femoral epiphysis; UK: United Kingdom; USA: United States of America.

Rosenbloom, 2013 [9]

Historical cohort analysis (1970s vs. 1990s)

476 children with type 1 diabetes (USA)

Prevalence of limited joint mobility (LJM) declined from ∼30% to ∼7% over two decades; LJM associated with poor metabolic control and ∼4-fold increased risk of microvascular complications.

Clarke, 1990 [11]

Cross-sectional

70 children with type 1 diabetes (UK)

LJM prevalence 31% by prayer sign; 7% using strict criteria. More frequent with older age and longer diabetes duration; no significant HbA1c correlation in this small cohort.

Montana, 1995 [12]

Cross-sectional

89 adolescents with type 1 diabetes (Spain)

LJM present in ∼42%; moderate–severe in 14%. Strong association with microalbuminuria, suggesting linkage with early diabetic microangiopathy.

Arkkila, 2003 [13]

Narrative review (pediatric data included)

Children and adults with diabetes mellitus

Summarized musculoskeletal complications of diabetes, including LJM and cheiroarthropathy; highlighted higher prevalence with longer disease duration and poor glycemic control.

McLean, 1995 [4]

Literature review and case series

Pediatric and adult hypothyroid patients

Hypothyroidism is associated with arthralgia, non-inflammatory joint effusions, and in children, epiphyseal dysgenesis and SCFE; synovial fluid typically viscous and acellular.

Gutch, 2013 [14]

Prospective cohort (6-month follow-up)

29 children with juvenile hypothyroidism (India)

Delayed bone age and metaphyseal thickening in all patients; short stature improved with therapy, but epiphyseal abnormalities persisted in >50% after 6 months; one SCFE case identified.

Lehmann 2006 [15]

Retrospective cohort

85 children with SCFE and endocrine disorders (USA)

Endocrine-related SCFE frequently bilateral and atypical; hypothyroidism and GH deficiency most common associations; recommended routine endocrine screening in atypical SCFE.

Karthikeyan, 2012 [16]

Case report

8-year-old girl with pseudohypoparathyroidism type 1b (UK)

Bilateral SCFE as presenting feature; associated with physeal widening and genu valgum; orthopedic fixation plus calcitriol led to physeal healing over 2 years.

Lindgren, 2023 [17]

Review with case series

90 patients with acromegaly (mostly adults; adolescents included, but pediatric subgroup not separately reported)

Highlighted endocrine etiologies (hypothyroidism, GH deficiency, hyperparathyroidism); endocrine-related SCFE occurred outside typical age/weight range and was frequently bilateral.

Dons, 1988 [18]

Retrospective cohort (long-term follow-up)

31 patients with long-term controlled acromegaly (mixed-age cohort; pediatric subgroup not separately reported)

Universal radiographic osteoarthritis at baseline; continued progression of hand and spine arthropathy despite biochemical remission in >80%; findings derive from a mixed-age cohort rather than a pediatric-only series.

Pelsma, 2021 [19]

Prospective cohort (9-year follow-up)

1 adolescent with Graves disease (Brazil)

Universal radiographic osteoarthritis at baseline; continued progression of hand and spine arthropathy despite biochemical remission in >80%.

Perini, 2019 [20]

Case report

16-year-old boy with Graves disease (Brazil)

Thyroid acropachy developed 2 years after radioiodine therapy; periosteal new bone formation and digital clubbing; rare pediatric manifestation.

Benina, 2023 [21]

Case series

Three children with primary hyperparathyroidism (Korea)

Presentations included bone pain, gait disturbance, and fractures; all due to parathyroid adenoma; musculoskeletal symptoms improved after surgery.

Lodish, 2018 [22]

Retrospective cohort

Children with endogenous Cushing syndrome (USA)

Vertebral fractures and musculoskeletal pain are common at diagnosis; bone density improved after cure, but some skeletal morbidity persisted.

↓ **Table 2.** Disorder-Specific Clinical Manifestations and Reported Prevalence of Arthropathy in Pediatric Endocrine Disorders
Endocrine disorder	Type of arthropathy/musculoskeletal involvement	Reported prevalence in children/adolescents	Key references (serial order)
GH: growth hormone; GHD: growth hormone deficiency; SCFE: slipped capital femoral epiphysis.
Type 1 diabetes mellitus	Limited joint mobility (cheiroarthropathy), predominantly hands; may extend to wrists and elbows	7–42% (historical cohorts up to 30–42%; contemporary cohorts ∼5–10%)	[11–13]
Juvenile hypothyroidism	Arthralgia, non-inflammatory joint effusions, epiphyseal dysgenesis; SCFE (rare but characteristic)	Arthralgia/effusions 10–30%; SCFE < 5% (largely case-based)	[4, 14, 16]
Hyperthyroidism (Graves disease)	Arthralgia, periosteal reaction; thyroid acropachy (very rare)	Arthralgia < 10%; acropachy < 1%	[20, 23]
Growth hormone excess (gigantism/acromegaly)	Degenerative arthropathy involving hands, spine, knees, and hips	70–80% in mixed-age cohorts including adolescents; pediatric-only prevalence unavailable	[18, 19]
Growth hormone deficiency	No primary inflammatory arthritis; increased risk of atypical SCFE and reduced bone strength	SCFE in GHD < 5% (overrepresented in atypical SCFE series)	[17]
Cushing syndrome (endogenous)	Bone pain, vertebral fractures, reduced mobility	Vertebral fractures 20–35%; musculoskeletal pain > 50%	[22, 24]
Primary hyperparathyroidism	Bone pain, gait disturbance, fractures; chondrocalcinosis (rare)	40–60% in small pediatric series	[21]
Pseudohypoparathyroidism	Skeletal dysplasia, occasional SCFE, functional joint limitation	Arthropathy uncommon; SCFE sporadic (case-based)	[16]

↓ Table 2. Disorder-Specific Clinical Manifestations and Reported Prevalence of Arthropathy in Pediatric Endocrine Disorders

Endocrine disorder

Type of arthropathy/musculoskeletal involvement

Reported prevalence in children/adolescents

Key references (serial order)

GH: growth hormone; GHD: growth hormone deficiency; SCFE: slipped capital femoral epiphysis.

Type 1 diabetes mellitus

Limited joint mobility (cheiroarthropathy), predominantly hands; may extend to wrists and elbows

7–42% (historical cohorts up to 30–42%; contemporary cohorts ∼5–10%)

[11–13]

Juvenile hypothyroidism

Arthralgia, non-inflammatory joint effusions, epiphyseal dysgenesis; SCFE (rare but characteristic)

Arthralgia/effusions 10–30%; SCFE < 5% (largely case-based)

[4, 14, 16]

Hyperthyroidism (Graves disease)

Arthralgia, periosteal reaction; thyroid acropachy (very rare)

Arthralgia < 10%; acropachy < 1%

[20, 23]

Growth hormone excess (gigantism/acromegaly)

Degenerative arthropathy involving hands, spine, knees, and hips

70–80% in mixed-age cohorts including adolescents; pediatric-only prevalence unavailable

[18, 19]

Growth hormone deficiency

No primary inflammatory arthritis; increased risk of atypical SCFE and reduced bone strength

SCFE in GHD < 5% (overrepresented in atypical SCFE series)

[17]

Cushing syndrome (endogenous)

Bone pain, vertebral fractures, reduced mobility

Vertebral fractures 20–35%; musculoskeletal pain > 50%

[22, 24]

Primary hyperparathyroidism

Bone pain, gait disturbance, fractures; chondrocalcinosis (rare)

40–60% in small pediatric series

[21]

Pseudohypoparathyroidism

Skeletal dysplasia, occasional SCFE, functional joint limitation

Arthropathy uncommon; SCFE sporadic (case-based)

[16]

↓ **Table 3.** Prevalence and Features of Diabetic Arthropathy (Limited Joint Mobility) in Children With Type 1 Diabetes
Study	Year	No. of diabetic patients (age)	Prevalence of LJM	Notable associations
HbA1c: glycated hemoglobin; LJM: limited joint mobility.
Rosenbloom et al [9] (historical cohort/era comparison)	1976–1998	182 (7–18 years) in 1976–1978; 294 in 1998	∼30% (1970s) → ∼7% (1998)	LJM associated with about four-fold increased long-term risk of microvascular complications; higher cumulative glycemic exposure markedly increased LJM risk.
Clarke et al [11] (cross-sectional)	1990	70 (8–17 years)	31% (prayer sign); 7% (strict criteria)	Higher prevalence with older age and longer diabetes duration; ∼12% of controls showed mild limitation, highlighting the need for standardized assessment.
Rosenbloom et al [5, 6, 9] (prospective natural history)	1981, 1982, 2013	309 (children and young adults, 1–28 years)	∼30% overall	LJM clustered in early-onset and pubertal-onset diabetes; associated with reduced linear growth in early cohorts; many cases asymptomatic on routine care.
Traisman et al [25] (screening study including siblings/controls)	1978	310 children with diabetes plus siblings/controls	8.4% (contractures)	Contractures also observed in siblings and controls, suggesting background susceptibility and reinforcing the importance of uniform diagnostic thresholds.
Campbell et al [26] (cross-sectional)	1985	Young patients with type 1 diabetes	Variable (criteria-dependent)	LJM associated with microvascular complications, supporting its role as a marker of cumulative metabolic burden rather than isolated joint disease.

↓ Table 3. Prevalence and Features of Diabetic Arthropathy (Limited Joint Mobility) in Children With Type 1 Diabetes

Study

Year

No. of diabetic patients (age)

Prevalence of LJM

Notable associations

HbA1c: glycated hemoglobin; LJM: limited joint mobility.

Rosenbloom et al [9] (historical cohort/era comparison)

1976–1998

182 (7–18 years) in 1976–1978; 294 in 1998

∼30% (1970s) → ∼7% (1998)

LJM associated with about four-fold increased long-term risk of microvascular complications; higher cumulative glycemic exposure markedly increased LJM risk.

Clarke et al [11] (cross-sectional)

1990

70 (8–17 years)

31% (prayer sign); 7% (strict criteria)

Higher prevalence with older age and longer diabetes duration; ∼12% of controls showed mild limitation, highlighting the need for standardized assessment.

Rosenbloom et al [5, 6, 9] (prospective natural history)

1981, 1982, 2013

309 (children and young adults, 1–28 years)

∼30% overall

LJM clustered in early-onset and pubertal-onset diabetes; associated with reduced linear growth in early cohorts; many cases asymptomatic on routine care.

Traisman et al [25] (screening study including siblings/controls)

1978

310 children with diabetes plus siblings/controls

8.4% (contractures)

Contractures also observed in siblings and controls, suggesting background susceptibility and reinforcing the importance of uniform diagnostic thresholds.

Campbell et al [26] (cross-sectional)

1985

Young patients with type 1 diabetes

Variable (criteria-dependent)

LJM associated with microvascular complications, supporting its role as a marker of cumulative metabolic burden rather than isolated joint disease.

↓ **Table 4.** Thyroid-Related Arthropathy and Musculoskeletal Manifestations in Children and Adolescents
Study	Year	Population (age)	Thyroid disorder	Arthropathy/musculoskeletal phenotype	Reported prevalence	Notable associations/clinical implications
SCFE: slipped capital femoral epiphysis.
McLean & Podell [4]	1995	Pediatric and adult cases (narrative review)	Hypothyroidism	Non-inflammatory arthralgia, high-viscosity joint effusions, epiphyseal dysgenesis; hip involvement more prominent in children	Not pooled	Pediatric hypothyroidism may present with joint limitation and physeal disease rather than classic adult patterns; emphasizes endocrine testing in unexplained effusions.
Gutch et al [14]	2013	29 children (juvenile onset)	Hypothyroidism	Delayed bone age, metaphyseal thickening, epiphyseal abnormalities; occasional SCFE	Joint-specific prevalence not quantified	Growth improves with levothyroxine, but skeletal abnormalities may persist early after treatment, highlighting the importance of early diagnosis.
Moyer et al [27]	2016	2 children + literature review	Hypothyroidism	Atypical slipped capital femoral epiphysis	Rare (case-based)	Recommends thyroid screening in SCFE presenting outside the typical age or weight range or with delayed healing.
Ploegstra et al [23]	2011	15-year-old girl	Graves disease (on antithyroid drugs)	Antithyroid drug–induced arthritis	Very rare	Rapid resolution after drug withdrawal; important to distinguish from primary inflammatory arthritis.
Nihei et al [28]	2013	2 children (11 and 15 y)	Graves disease	Acute polyarthritis during methimazole therapy	Very rare	Supports early cessation of thionamides when severe arthritis develops.
Pereira et al [20]	2019	16-year-old boy	Graves disease	Thyroid acropachy (periosteal reaction, digital clubbing)	< 1%	Prolonged untreated hypothyroidism can cause severe locomotor disability, largely reversible with thyroid hormone replacement.
Tullu et al [29]	2003	2 children (7 y; 15 months)	Long-standing hypothyroidism	Kocher–Debré–Semelaigne syndrome with functional musculoskeletal limitation	Rare	Prolonged untreated hypothyroidism can cause severe locomotor disability, largely reversible with thyroid hormone.

↓ Table 4. Thyroid-Related Arthropathy and Musculoskeletal Manifestations in Children and Adolescents

Study

Year

Population (age)

Thyroid disorder

Arthropathy/musculoskeletal phenotype

Reported prevalence

Notable associations/clinical implications

SCFE: slipped capital femoral epiphysis.

McLean & Podell [4]

1995

Pediatric and adult cases (narrative review)

Hypothyroidism

Non-inflammatory arthralgia, high-viscosity joint effusions, epiphyseal dysgenesis; hip involvement more prominent in children

Not pooled

Pediatric hypothyroidism may present with joint limitation and physeal disease rather than classic adult patterns; emphasizes endocrine testing in unexplained effusions.

Gutch et al [14]

2013

29 children (juvenile onset)

Hypothyroidism

Delayed bone age, metaphyseal thickening, epiphyseal abnormalities; occasional SCFE

Joint-specific prevalence not quantified

Growth improves with levothyroxine, but skeletal abnormalities may persist early after treatment, highlighting the importance of early diagnosis.

Moyer et al [27]

2016

2 children + literature review

Hypothyroidism

Atypical slipped capital femoral epiphysis

Rare (case-based)

Recommends thyroid screening in SCFE presenting outside the typical age or weight range or with delayed healing.

Ploegstra et al [23]

2011

15-year-old girl

Graves disease (on antithyroid drugs)

Antithyroid drug–induced arthritis

Very rare

Rapid resolution after drug withdrawal; important to distinguish from primary inflammatory arthritis.

Nihei et al [28]

2013

2 children (11 and 15 y)

Graves disease

Acute polyarthritis during methimazole therapy

Very rare

Supports early cessation of thionamides when severe arthritis develops.

Pereira et al [20]

2019

16-year-old boy

Graves disease

Thyroid acropachy (periosteal reaction, digital clubbing)

< 1%

Prolonged untreated hypothyroidism can cause severe locomotor disability, largely reversible with thyroid hormone replacement.

Tullu et al [29]

2003

2 children (7 y; 15 months)

Long-standing hypothyroidism

Kocher–Debré–Semelaigne syndrome with functional musculoskeletal limitation

Rare

Prolonged untreated hypothyroidism can cause severe locomotor disability, largely reversible with thyroid hormone.

↓ **Table 5.** Growth Hormone (GH) Excess– and Deficiency–Related Arthropathy in Children and Adolescents: Key Clinical Patterns and Representative Evidence
Study	Year	Study type	Population (GH disorder)	Arthropathy/musculoskeletal phenotype	Key findings relevant to arthropathy
GH: growth hormone; GHD: growth hormone deficiency; IGF-1: insulin-like growth factor-1; OA: osteoarthritis; SCFE: slipped capital femoral epiphysis.
Rostomyan et al [31]	2015	Multicenter cohort	Pituitary gigantism (pediatric-onset GH excess)	Arthralgia and early degenerative joint changes accompanying rapid linear growth and soft-tissue overgrowth	Large international cohort describing the clinical burden of pediatric-onset GH excess; musculoskeletal complaints, including joint pain, are frequent and often prompt evaluation alongside accelerated growth.
Beckers et al [32]	2018	Evidence synthesis/review	Pituitary gigantism (pediatric-onset GH excess)	Overgrowth-related joint pain; propensity to early osteoarthropathy in longstanding GH excess	Demonstrated that prolonged GH/IGF-1 excess drives cartilage and periarticular tissue hypertrophy, predisposing to early degenerative arthropathy and supporting proactive musculoskeletal assessment.
Claessen et al [33]	2017	Comparative MRI study	Active vs. controlled acromegaly (mixed-age cohort; disease biology relevant to adolescent-onset GH excess)	“Acromegalic arthropathy” with knee cartilage thickening, osteophytosis, and OA-like changes	Showed high prevalence of structural joint abnormalities; some cartilage features improved with biochemical control, whereas structural damage often persisted, informing mechanisms relevant to pediatric-onset disease.
Colao et al [34]	2017	Narrative review with clinical synthesis	Acromegaly (mixed-age clinical synthesis)	Progressive degenerative arthropathy affecting hands, spine, hips, and knees	Highlighted that GH excess–related arthropathy may progress despite biochemical remission, supporting the concept of partially irreversible joint disease once established.
Blethen et al [35]	1996	Registry safety analysis	16,514 children receiving recombinant GH (NCGS)	Slipped capital femoral epiphysis (SCFE) as GH therapy–associated hip arthropathy	Identified SCFE as a rare but clinically important orthopedic complication during GH therapy, emphasizing the need for vigilance for hip or knee symptoms in growing children.
Darendeliler et al [36]	2007	Nationwide population-based cohort	80,769 children with endocrinopathy and 191,004 without endocrinopathy	SCFE as an endocrinopathy-associated growth-plate complication	SCFE incidence was approximately fourfold higher in children with endocrinopathy than in children without endocrinopathy (37.1 vs. 9.0 per 100,000). Among endocrinopathies, growth hormone deficiency had the highest SCFE incidence (583.8 per 100,000), supporting risk stratification and early hip evaluation.
Hwang et al [30]	2024	Children with endocrinopathy: 80,769	Endocrinopathy-associated SCFE: 30/191 (16%)	SCFE incidence was ∼4× higher in children with endocrinopathy vs without: 37.1 vs. 9.0 per 100,000	Among endocrinopathies, growth hormone deficiency (GHD) had the highest SCFE incidence: 583.8 per 100,000

↓ Table 5. Growth Hormone (GH) Excess– and Deficiency–Related Arthropathy in Children and Adolescents: Key Clinical Patterns and Representative Evidence

Study

Year

Study type

Population (GH disorder)

Arthropathy/musculoskeletal phenotype

Key findings relevant to arthropathy

GH: growth hormone; GHD: growth hormone deficiency; IGF-1: insulin-like growth factor-1; OA: osteoarthritis; SCFE: slipped capital femoral epiphysis.

Rostomyan et al [31]

2015

Multicenter cohort

Pituitary gigantism (pediatric-onset GH excess)

Arthralgia and early degenerative joint changes accompanying rapid linear growth and soft-tissue overgrowth

Large international cohort describing the clinical burden of pediatric-onset GH excess; musculoskeletal complaints, including joint pain, are frequent and often prompt evaluation alongside accelerated growth.

Beckers et al [32]

2018

Evidence synthesis/review

Pituitary gigantism (pediatric-onset GH excess)

Overgrowth-related joint pain; propensity to early osteoarthropathy in longstanding GH excess

Demonstrated that prolonged GH/IGF-1 excess drives cartilage and periarticular tissue hypertrophy, predisposing to early degenerative arthropathy and supporting proactive musculoskeletal assessment.

Claessen et al [33]

2017

Comparative MRI study

Active vs. controlled acromegaly (mixed-age cohort; disease biology relevant to adolescent-onset GH excess)

“Acromegalic arthropathy” with knee cartilage thickening, osteophytosis, and OA-like changes

Showed high prevalence of structural joint abnormalities; some cartilage features improved with biochemical control, whereas structural damage often persisted, informing mechanisms relevant to pediatric-onset disease.

Colao et al [34]

2017

Narrative review with clinical synthesis

Acromegaly (mixed-age clinical synthesis)

Progressive degenerative arthropathy affecting hands, spine, hips, and knees

Highlighted that GH excess–related arthropathy may progress despite biochemical remission, supporting the concept of partially irreversible joint disease once established.

Blethen et al [35]

1996

Registry safety analysis

16,514 children receiving recombinant GH (NCGS)

Slipped capital femoral epiphysis (SCFE) as GH therapy–associated hip arthropathy

Identified SCFE as a rare but clinically important orthopedic complication during GH therapy, emphasizing the need for vigilance for hip or knee symptoms in growing children.

Darendeliler et al [36]

2007

Nationwide population-based cohort

80,769 children with endocrinopathy and 191,004 without endocrinopathy

SCFE as an endocrinopathy-associated growth-plate complication

SCFE incidence was approximately fourfold higher in children with endocrinopathy than in children without endocrinopathy (37.1 vs. 9.0 per 100,000). Among endocrinopathies, growth hormone deficiency had the highest SCFE incidence (583.8 per 100,000), supporting risk stratification and early hip evaluation.

Hwang et al [30]

2024

Children with endocrinopathy: 80,769

Endocrinopathy-associated SCFE: 30/191 (16%)

SCFE incidence was ∼4× higher in children with endocrinopathy vs without: 37.1 vs. 9.0 per 100,000

Among endocrinopathies, growth hormone deficiency (GHD) had the highest SCFE incidence: 583.8 per 100,000

↓ **Table 6.** Overall Risk of Bias Across Studies Included in the Review
Overall risk of bias	Reference numbers	Main study types represented	Brief quality summary
SCFE: slipped capital femoral epiphysis.
Low risk	5–7, 19, 22, 24, 30, 31, 33, 35, 36	Large cohorts, population-based studies, prospective longitudinal studies, registry analyses, comparative imaging studies	Strong population definition, clear outcome ascertainment, and consistent exposure assessment. Longitudinal follow-up and population-based designs reduce selection bias; residual confounding possible but generally well controlled.
Moderate risk	8, 11, 12, 14, 15, 17, 18, 21	Retrospective and prospective cohorts, cross-sectional studies, imaging studies, medium-sized clinical series	Non-randomized designs with variable outcome definitions (e.g., LJM criteria, arthropathy phenotypes, SCFE ascertainment) and incomplete adjustment for confounders such as disease duration or severity. Generally robust clinical populations with biologically plausible and clinically anchored outcomes.
High risk	1–4, 9, 10, 13, 16, 20, 23, 25–29, 32, 34	Narrative reviews, expert syntheses, case reports/series, very small uncontrolled cohorts	High susceptibility to selection and reporting bias; limited generalizability; often descriptive without standardized outcome measurement. Particularly valuable for rare phenotypes (e.g., thyroid acropachy, antithyroid drug–induced arthritis, pseudohypoparathyroidism-related SCFE, Kocher–Debré–Semelaigne syndrome) but not suitable for prevalence estimation.

↓ Table 6. Overall Risk of Bias Across Studies Included in the Review

Overall risk of bias

Reference numbers

Main study types represented

Brief quality summary

SCFE: slipped capital femoral epiphysis.

Low risk

5–7, 19, 22, 24, 30, 31, 33, 35, 36

Large cohorts, population-based studies, prospective longitudinal studies, registry analyses, comparative imaging studies

Strong population definition, clear outcome ascertainment, and consistent exposure assessment. Longitudinal follow-up and population-based designs reduce selection bias; residual confounding possible but generally well controlled.

Moderate risk

8, 11, 12, 14, 15, 17, 18, 21

Retrospective and prospective cohorts, cross-sectional studies, imaging studies, medium-sized clinical series

Non-randomized designs with variable outcome definitions (e.g., LJM criteria, arthropathy phenotypes, SCFE ascertainment) and incomplete adjustment for confounders such as disease duration or severity. Generally robust clinical populations with biologically plausible and clinically anchored outcomes.

High risk

1–4, 9, 10, 13, 16, 20, 23, 25–29, 32, 34

Narrative reviews, expert syntheses, case reports/series, very small uncontrolled cohorts

High susceptibility to selection and reporting bias; limited generalizability; often descriptive without standardized outcome measurement. Particularly valuable for rare phenotypes (e.g., thyroid acropachy, antithyroid drug–induced arthritis, pseudohypoparathyroidism-related SCFE, Kocher–Debré–Semelaigne syndrome) but not suitable for prevalence estimation.