Growth Hormone Treatment Research Articles

Exploring the sex difference in cardiovascular risk during growth hormone therapy in adults.

Given the previously identified sex differences in cardiovascular (CV) morbidity and mortality in patients with growth hormone deficiency (GHD) receiving GH replacement therapy (GHRT), our aim is to investigate sex-specific differences in the efficacy of (long-term) GHRT on CV risk profile and disease in subjects with GHD. Our hypothesis is that women will experience less beneficial effects than men. Retrospective nationwide cohort study. We compared all men (n = 1335) and women (n = 1251) with severe GHD registered in the Dutch National Registry of GH Treatment in Adults database with respect to CV risk profile and morbidity at baseline and during follow-up. Men had a more unfavourable CV risk profile at baseline. During the first years of GHRT, the reduction in waist circumference, waist-to-hip ratio, total cholesterol, and triglyceride levels was greater in men than in women (all P < .05). Between-sex differences in effects during later follow-up were less clear. No sex differences were found in the risk of developing non-fatal cardiovascular or cerebrovascular diseases during GHRT. Our results suggest that men with GHD did indeed experience more beneficial effects of GHRT on body composition and lipoprotein metabolism than women, at least in the early years of treatment. Also, the more unfavourable CV risk profile at baseline in men did not translate into a sex difference in the risk of developing CV and cerebrovascular morbidity during GHRT.

Bioethical, medical, and social problems in children with growth hormone deficiency

Background. Medical and practical advancements have brought about new possibilities for providing healthcare to people, but with it comes new bioethical challenges. In many pediatric medical institutions, consultations on pediatric ethics have become common practice. However, the bioethical problems related to short children have not been studied enough yet. The purpose of this study is to identify and analyze bioethical, medical, and social issues in children with growth hormone deficiency (GHD), which can potentially hinder timely diagnosis and adherence to replacement therapy. Materials and methods. The identification of bioethical, medical, and social problems was conducted at the Odesa Regional Children’s Hospital between 2012 and 2020. The study involved a cohort of 94 children with GHD and short stature (SDS 3.4 ± 0.1), aged 7.2 ± 0.4 years, as well as their parents (124 individuals). The study was based on a questionnaire survey, history taking, interviews, objective examination of patients, and analysis of medical records. Results. The study found evidence of violations of the Hippocratic principle of help and assistance (“do good”) in the form of delayed or incorrect diagnosis in 10.6 % of cases and incomplete adherence to local protocols for managing sick children in 6.4 % of cases. Violations of the Hippocratic principle of non-harm (“first, do no harm”) were evidenced by adverse events (16.0 %) and serious adverse events (3.2 %) during replacement therapy. Children with GHD were subject to violations of social justice, such as neglect (8.5 %), socio-economic problems in the family (12.8 %), and external environmental restrictions (9.6 %). Violations of the personal autonomy of children with GНD inclu­ded physical and psychological abuse in the family (29.8 and 38.3 % of cases, respectively), stigmatization (25.5 %), school bullying (27.2 %), medical neglect (5.3 %), medical paternalism (6.4 %), and overprotection (10.6 %). Conclusions. In the management of children with GHD, various bioethical, medical, and social issues have come to light. Low adherence to recombinant human growth hormone therapy can be considered an independent bioethical problem associated with medical paternalism and medical neglect.

Transient Isolated, Idiopathic Growth Hormone Deficiency-A Self-Limiting Pediatric Disease with Male Predominance or a Diagnosis Based on Uncertain Criteria? Lesson from 20 Years' Real-World Experience with Retesting at One Center.

In the majority of children with growth hormone (GH) deficiency (GHD), normal GH secretion may occur before the attainment of final height. The aim of the study was to assess the incidence of persistent and transient GHD and the effectiveness of recombined human GH (rhGH) therapy in children with isolated, idiopathic GHD with respect to the moment of therapy withdrawal and according to different diagnostic criteria of GHD. The analysis included 260 patients (173 boys, 87 girls) with isolated, idiopathic GHD who had completed rhGH therapy and who had been reassessed for GH and IGF-1 secretion. The incidence of transient GHD with respect to different pre- and post-treatment criteria was compared together with the assessment of GH therapy effectiveness. The incidence of transient GHD, even with respect to pediatric criteria, was very high. Normal GH secretion occurred before the attainment of near-final height. Application of more restricted criteria decreased the number of children diagnosed with GHD but not the incidence of transient GHD among them. Poor response to GH therapy was observed mainly in the patients with normal IGF-1 before treatment, suggesting that their diagnosis of GHD may have been a false positive. Further efforts should be made to avoid the overdiagnosis GHD and the overtreatment of patients.

Clinical Features and Analysis in Pituitary Stalk Interruption Syndrome.

Pituitary stalk interruption syndrome (PSIS) is characterized by the absence of pituitary stalk, pituitary hypoplasia, and ectopic posterior pituitary. Because the etiology and clinical cognition of PSIS remain elusive, we analyzed the clinical features of PSIS in Chinese patients. A retrospective analysis was conducted on the clinical presentation, laboratory data, imaging examination, and management of 24 PSIS inpatients from our center over 10 years. Among the 24 PSIS patients, there were 22 males (91.7%) and 2 females (8.3%). Growth hormone deficiency was present in all 24 cases (100%), hypogonadism in 24 cases (100%), secondary adrenal insufficiency in 22 cases (91.2%), and hypothyroidism in 21 cases (87.5%). 20 cases (83.3%) of PSIS patients exhibited deficiencies in four anterior pituitary hormones, 3 cases (12.5%) exhibited deficiencies in three anterior pituitary hormones, and 1 case (4.2%) exhibited deficiencies in two anterior pituitary hormones, with none exhibiting deficiencies in posterior pituitary hormones. Among the 24 PSIS patients, 12 had a history of growth hormone therapy before admission, and 12 had no such history. Additionally, 19 cases (79.2%) with PSIS were complicated by dyslipidemia, 15 cases (62.5%) were complicated by nonalcoholic fatty liver disease, and 9 cases (37.5%) were complicated by hyperuricemia. PSIS often presents with growth retardation and hypogonadotropic hypogonadism, but in some cases, short stature is not exhibited. PSIS is prone to complications such as dyslipidemia, nonalcoholic fatty liver disease, and hyperuricemia, increasing the risk of cardiovascular and cerebrovascular diseases. In clinical practice, the diagnostic ability of PSIS should be improved, and pituitary function and complications should be evaluated in a timely manner to avoid delayed treatment.

Cerebral white matter hyperintensities in adults born small for gestational age at 12 years after cessation of childhood growth hormone treatment: a prospective cohort study including untreated controls

Increased cerebrovascular morbidity was reported in adults born small for gestational age (SGA) who were treated with growth hormone (GH) during childhood compared to the general population. Yet, previous studies lacked an appropriate control group which is a major limitation. We prospectively studied cerebral white matter hyperintensities (WMHs) in adults born SGA at 12 years after cessation of childhood GH-treatment (SGA-GH), compared to appropriate controls. In this prospective cohort study, performed between May 2016 and December 2020, total WMHs, periventricular WMHs (PVWMHs) and deep WMHs (DWMHs) were the primary outcomes of the study, they were qualitatively assessed using 3Tesla (T) Magnetic Resonance Imaging (MRI) and scored using the Fazekas scale in SGA-GH adults and in 3 untreated control groups: adults born SGA with persistent short stature (SGA-S), adults born SGA with spontaneous catch-up growth to a normal height (SGA-CU) and adults born appropriate for gestational age with a normal height (AGA). Regression analyses were performed in the total cohort to evaluate the associations of GH-treatment and birth characteristics with WMHs. 297 adults were investigated (91 SGA-GH, 206 controls). Prevalence of total WMHs was 53.8% (95% CI 43.1-64.3) in SGA-GH, 40.5% (95% CI 25.6-56.7) in SGA-S, 73.9% (95% CI 61.9-83.7) in SGA-CU and 41.1% (95% CI 31.1-51.6) in AGA adults. No statistically significant differences in total WMHs, PVWMHs and DWMHs were found between SGA-GH compared to SGA-S and AGA adults. Highest prevalence of all type of WMHs was found in SGA-CU adults compared to all groups. Higher prevalence of total WMHs was associated with lower birth weight standard deviation score (SDS), but not with GH-treatment. Our findings suggest that GH-treatment in children born SGA has no negative impact on the prevalence of all type of WMHs at 12 years after GH cessation compared to appropriate controls. SGA-CU adults had the highest prevalence of all type of WMHs around age 30 years. Novo Nordisk.

Heightism, growth hormone treatment, and social functioning: a holistic approach to a persistent clinical challenge.

Use of recombinant human growth hormone (rhGH) treatment to increase height in children with non-growth hormone deficient short stature is becoming more common. Yet, the evidence to support the notion that augmenting height directly leads to increased well being, specifically psychosocial well being, is inconsistent, with high-quality evidence lacking. Review of recent studies demonstrates that the association between height augmentation and psychosocial well being is complex. The direct contribution of height to well being may be less than the current model of clinical care of short stature assumes. Rather, the new studies provide evidence to support a role for psychosocial factors, including height-related beliefs, social support, and coping skills, in promoting psychosocial well being, specifically quality of life and self-esteem. Clinical care of short stature would benefit from incorporating a holistic model of care that considers psychosocial interventions in addition to, or instead of, rhGH treatment.

Are Young People with Turner Syndrome Who Have Undergone Treatment with Growth and Sex Hormones at Higher Risk of Metabolic Syndrome and Its Complications?

Metabolic syndrome (MetS), characterized by visceral obesity, glucose abnormalities, hypertension and dyslipidemia, poses a significant risk of diabetes and cardiovascular disease. Turner syndrome (TS), resulting from X chromosome abnormalities, carries health complications. Despite growing evidence of an increased risk of MetS in women with TS, its prevalence and risk factors remain under investigation. These considerations are further complicated by the varying timing and dosages of treatment with growth hormone and sex hormones. We conducted a cross-sectional study comparing 44 individuals with TS with 52 age-matched control subjects. Growth hormone treatment in the study group was administered for varying lengths of time, depending on clinical response. We collected anthropometric, metabolic, endocrine and body composition data. Statistical analyses included logistic regression. Baseline characteristics, including age, BMI and height, were comparable between the TS and control groups. Hormonally, individuals with TS showed lower levels of testosterone, DHEA-S, and cortisol, as well as elevated FSH. Lipid profiles indicated an atherogenic profile, and the body composition analysis showed increased visceral adipose tissue in those with TS. Other metabolic abnormalities were common in individuals with TS too, including hypertension and impaired fasting glucose levels. The risk of MetS components was assessed in subgroups according to karyotypes: monosomy 45X0 vs. other mosaic karyotypes. Logistic regression analysis showed a significant association between increased visceral adipose tissue in subjects with TS. Those with metabolic complications tended to have less muscle strength compared to those without these complications in both the study and control groups. This study highlights the unique metabolic and cardiovascular risk profile of individuals with TS, characterized by atherogenic lipids, higher levels of visceral adipose tissue and increased metabolic abnormalities. These findings underscore the importance of monitoring metabolic health in individuals with TS, regardless of age, BMI or karyotype, and suggest the potential benefits of lifestyle modification, building more muscle strength, and weight control strategies. Further research is needed to better understand and address the metabolic challenges faced by women with TS.

Exploring the cardiovascular effects of recombinant human growth hormone therapy: a prospective study on endothelin-1 and asymmetric dimethyl arginine in adults with growth hormone deficiency

Exploring the cardiovascular effects of recombinant human growth hormone therapy: a prospective study on endothelin-1 and asymmetric dimethyl arginine in adults with growth hormone deficiency

Effects of recombinant growth hormone treatment on metabolic fitness, body composition and echocardiographic parameters in a population of patients with overweight or obesity and adult GH deficiency

Effects of recombinant growth hormone treatment on metabolic fitness, body composition and echocardiographic parameters in a population of patients with overweight or obesity and adult GH deficiency

Characterization of patients stopping GH therapy for childhood-onset growth hormone deficiency in belgium - luxemburg

Characterization of patients stopping GH therapy for childhood-onset growth hormone deficiency in belgium - luxemburg

Linear growth and response to GH therapy in short children with normal vs low IGF1 level and normal BMI at presentation

Linear growth and response to GH therapy in short children with normal vs low IGF1 level and normal BMI at presentation

The shadow side of growth: understanding growth hormone therapy’s role in slipped capital femoral epiphysis

The shadow side of growth: understanding growth hormone therapy’s role in slipped capital femoral epiphysis

Growth Hormone Therapy in a Child with Fetal Alcohol Syndrome: Personal Experience with Literature Review

Introduction: Fetal alcohol syndrome (FAS) is associated with a positive maternal history of drinking during pregnancy and the presence of characteristic dysmorphic features due to alcohol teratogenic effect. No evidence is yet available regarding the use of growth hormone (GH) for children with FAS for whom GH deficiency has not been confirmed. Case Presentation: We have highlighted an improvement in auxological parameters of a child with FAS and normal GH stimulation tests, using a GH dosage similar to that used in idiopathic GH deficit, without side effects. Conclusion: GH therapy in children with FAS may lead to an improvement in growth rate and an increase in final height, although, this condition is not included in the specific recommendations for use of GH. Prolonged follow-up and prospective studies are needed to evaluate long-term efficacy and monitor any possible onset of side effects.

Carotid Intima-Media Thickness and Cardiometabolic Profile in Turner Syndrome: A Cross-Sectional Study.

Turner syndrome (TS), one of the most common chromosomal abnormalities in females, often results in adult cardiovascular and metabolic complications. Information on pediatric age is scarce. This study aimed to compare the presence of cardiometabolic risk factors in children with TS and healthy controls. This is a cross-sectional study comparing patients with TS to age-matched healthy controls, regarding cardiometabolic risk factors includinglipid profile, fasting glucose, insulin resistance, body composition, body mass index, blood pressure, and carotid intima-media thickness (cIMT). We included nine TS patients and ninecontrols with a median age of 13 years (9-14 years). Three TS patients and three controls were prepubertal. All TS patients received growth hormone treatment (GHT), median treatment of six years (3-10 years); four patients underwent treatment with estradiol. No statistically significant differences were detected between TS patients and controls regarding body mass index (BMI), cholesterol levels, and insulin resistance. cIMT indexed to body surface area showed no significant differences between TS patients and controls (0.37 vs 0.35 mm/m2, respectively, p=0.605). TS patients had lower body fat levels (7.2% vs 34.9%, p=0.004). On the other hand, TS patients had higher levels of systolic (z-score 1.04 vs -0.08, p=0.001) and diastolic (z-score 1.08 vs 0.33, p=0.031) blood pressure (BP) and aspartate (AST) and alanine (ALT) aminotransferase levels (26 vs 20 U/L, p=0.008 and 19 vs 14 U/L, p=0.004, respectively). Patients with TS, all submitted to GHT, had lower body fat levels compared with controls, despite similar BMI. Although we found no differences in cIMT between the two groups, young girls with TS had higher BP and transaminase levels. Early anthropometric, cardiovascular, and analytical monitoring of patients with TS is essential to detect abnormalities and prevent further complications.

The impact of growth hormone (GH) therapy on glucose metabolism: A narrative review mainly focused on GH-deficient (GHD) children and adolescents

Introduction: Growth hormone (GH) deficiency (GHD) in children and adolescents is traditionally managed with GH therapy, which, while effective for promoting growth, poses potential metabolic repercussions, particularly concerning glucose metabolism. This review delineates the complex interplay between GH therapy, insulin sensitivity, and glucose homeostasis. Objective: To synthesize existing literature on the effects of GH therapy on glucose metabolism, insulin secretion, and insulin sensitivity in GH-deficient pediatric populations, aiming to illuminate the nuanced metabolic consequences and to optimize therapeutic outcomes. Results: The reviewed studies illuminate a complex influence of GH therapy on metabolic parameters. While GH promotes growth and improves body composition, it may concurrently impair insulin sensitivity, elevate fasting glucose levels, and, in some cases, induce glucose intolerance. However, the dysglycemic effect during GH therapy appears to be transient and reversible on discontinuation of therapy. The counterbalancing role of insulin-like growth factor 1 (IGF-1) and its contribution to maintaining glucose homeostasis is also highlighted, illustrating a complex metabolic interplay induced by GH therapy. Discussion: The findings underscore the variability in individual metabolic responses to GH therapy. The balance between GH-induced insulin resistance and IGF-1-mediated insulin sensitivity is crucial. Monitoring and adjusting GH therapy based on glycemic response is imperative to prevent adverse metabolic outcomes. Conclusion: GH therapy in GH-deficient children and adolescents requires careful consideration of its metabolic effects. Personalized treatment strategies and vigilant monitoring of glucose metabolism are essential to optimize therapeutic outcomes and minimize the risk of metabolic complications. Further research is warranted to establish comprehensive guidelines for managing the metabolic aspects of GH therapy in this vulnerable population.

Cerebral stroke-induced neurogenesis: insights and therapeutic implications

Stroke, one of the leading causes of global morbidity and mortality, results from disrupted cerebral blood circulation, leads to cellular damage or death. Ischemic stroke, the predominant subtype, relies mainly on recombinant tissue plasminogen activator (rtPA) and endovascular thrombectomy for the treatment. Neurological impairments following ischemic stroke highlight the importance of understanding the interplay between neuroinflammation and neurogenesis in brain repair. Research reveals a complex relationship, where inflammation both promotes and hinders neurogenesis, impacting post-stroke outcomes. The subventricular zone (SVZ) of striatum and sub granular zone (SGZ) in hippocampus play pivotal roles in adult neurogenesis, with distinct characteristics and functions. SVZ neurogenesis involves neuroblast progenitors migrating to the olfactory bulb, while SGZ facilitates granule cell generation for hippocampal function. Understanding the intricate processes of neuroinflammation, neurogenesis, and angiogenesis is crucial for developing effective stroke therapeutics. Promising avenues include drug therapy, selective serotonin reuptake inhibitors, antibody therapy, angiogenesis stimulation, growth factor therapy, hormone therapy, miRNAs, extracellular vesicles, and neuroprotective agents. Stem cell therapy, exploring various cell types, holds potential for neuronal replacement and recovery. In conclusion, deciphering the roles of SVZ and SGZ in neurogenesis, unraveling the complexity of neuroinflammation’s impact on repair, and exploring diverse therapeutic approaches highlight the need for comprehensive investigations to enhance stroke outcomes. The multifaceted landscape of stroke therapeutics presents challenges, but ongoing research offers promising avenues for bridging the gap between preclinical findings and clinical treatments.

Comprehensive Insights Into Pediatric Craniopharyngioma: Endocrine and Metabolic Profiles, Treatment Challenges, and Long-term Outcomes from a Multicenter Study

Craniopharyngiomas (CPG) have complex treatment challenges due to their proximity to vital structures, surgical and radiotherapeutic complexities, and the tendency for recurrence. The aim of this study was to identify the prevalence of endocrine and metabolic comorbidities observed during initial diagnosis and long-term follow-up in a nationwide cohort of pediatric CPG patients. A further aim was to highlight the difficulties associated with CPG management. Sixteen centers entered CPG patients into the ÇEDD NET data system. The clinical and laboratory characteristics at presentation, administered treatments, accompanying endocrine, metabolic, and other system involvements, and the patient’s follow-up features were evaluated. Of the 152 evaluated patients, 64 (42.1%) were female. At presentation, the mean age was 9.1±3.67, ranging from 1.46 to 16.92, years. The most common complaints at presentation were headache (68.4%), vision problems (42%), short stature (15%), and nausea and vomiting (7%). The surgical procedures were gross total resection (GTR) in 97 (63.8%) and subtotal resection in 55 (36.2%). Radiotherapy (RT) was initiated in 11.8% of the patients. Histopathological examination reported 92% were adamantinamatous type and 8% were papillary type. Postoperatively, hormone abnormalities consisted of thyroid-stimulating hormone (92.1%), adrenocorticotropic hormone (81%), antidiuretic hormone (79%), growth hormone (65.1%), and gonadotropin (43.4%) deficiencies. Recombinant growth hormone treatment (rhGH) was initiated in 27 (17.8%). The study showed hesitancy among physicians regarding rhGH. The median survival without relapse was 2.2 years. Median (range) time of relapse was 1.82 (0.13-10.35) years. Relapse was related to longer followups and reduced GTR rates. The median follow-up time was 3.13 years. Among the last follow-up visits, the prevalence of obesity was 38%, but of these, 46.5% were already obese at diagnosis. However, 20% who were not obese at baseline became obese on follow-up. Permanent visual impairment was observed in 26 (17.1%), neurological deficits in 13 (8.5%) and diabetes mellitus in 5 (3.3%) patients. Recurrence was predominantly due to incomplete resection and the low rate of postoperative RT. Challenges emerged for multidisciplinary regular follow ups. It is suggested that early interventions, such as dietary restrictions and increased exercise to prevent obesity, be implemented.

Potential for Optimization of Growth Hormone Treatment in Children with Growth Hormone Deficiency, Small for Gestational Age, and Turner Syndrome in Germany: Data from the PATRO® Children Study

Introduction: Growth hormone (GH) treatment in children with growth hormone deficiency (GHD), short children born small for gestational age (SGA), and Turner syndrome (TS) is well established. However, a variety of parameters are still under discussion to achieve optimal growth results and efficiency of GH use in real-world treatment. Methods: German GH-treatment naïve patients of the PATRO Children database were grouped according to their start of treatment into groups of 3 years from 2007 to 2018. Time trends in age, gender, GH dose, height standard deviation score (SDS), first-year growth response, and Index of Responsiveness (IoR) were investigated in children with GHD, short children born SGA, and TS starting GH treatment in the German patient population of the PATRO Children database from 2007 to 2018 to determine specific parameters for GH treatment optimization. Results: All patient groups started GH treatment at a relatively high chronological age (2007–2009: GHD 8.33 ± 3.19, SGA 7.32 ± 2.52, TS 8.65 ± 4.39) with a slight but not significant trend towards younger therapy start up to 2016–2018 (GHD 8.04 ± 3.36, SGA 6.67 ± 2.65, TS 7.85 ± 3.38). In the GHD and SGA groups, female patients were underrepresented compared to male patients (GHD 32.3%, SGA 43.6%) with no significant change over the 4 time periods. Patients with GHD started GH treatment at a low dose (0.026 mg/kg/day). In SGA and TS patients, GH therapy was started below the registered dose recommendation (30.0 μg/kg/day and 33.7 μg/kg/day, respectively). In the first year of treatment, the mean GH dose was increased moderately (GHD: 30.7, SGA: 35.7, TS: 40.8 μg/kg/day). There was no significant change of GH dosing over time from 2007 to 2018. The IoR was comparable between time-groups for all 3 diagnoses. Discussion: This study shows potential for improvement of GH treatment results in GHD, SGA, and TS patients in terms of early dose adjustment and younger age at the start of treatment. This is in accordance with important parameters used in prediction models.

Exogenous growth hormone (GH) increases dimension and reduces strength of vertebrae in Atlantic salmon (Salmo salar)

Growth hormone (GH) administration increases bone strength in rats, mainly through alterations of the dimensional proportions of vertebrae. However, similar knowledge is lacking in other clades. In order to pursue this, Atlantic salmon were fed diets with high or low vitamin C and E and administered a slow-release implant of bovine GH.While neither the diets or the GH treatment affected growth, GH reduced condition factor and carcass-somatic index, and increased the hepatosomatic and visceral-somatic indexes. GH had an impact on the dimensional proportions of the vertebrae and increased the relative dorso-ventral and lateral vertebra diameters. Moreover, GH decreased the mechanical strength of the vertebra, both with (modulus of elasticity, failure point) and without (stiffness) normalizing the mechanical data for the dimensions of the vertebrae. Diet did not impact on the vertebra morphometry or mechanical strength. RNA-seq of vertebra centra show that several genes associated with bone growth and remodelling were affected by GH, while there was an interactive effect between diet vitamin level and GH on several genes associated with lipid metabolism.The data may suggest that exogenous GH affects the bone cellular mechanisms of Atlantic salmon postsmolts in such a way that their vertebrae increase in diameter but not length, not disturbing growth in body length. The GH and diet effects on lipid metabolism associated genes indicate a complex regulation of the lipids stored inside the vertebral column by endocrine and nutritional factors.

Pathological Fractures in Patients Affected by Pycnodysostosis: A Case Series.

Background/Objectives: Pycnodysostosis is a rare genetic disorder causing skeletal dysplasia. It is determined by a gene mutation leading to cathepsin K deficiency and predisposes a patient to osteosclerosis, resulting in increased bone fragility. The altered bone quality typical of this disease is responsible for an increased risk of fractures. The purpose of our study was to evaluate the orthopedic manifestations and potential pitfalls in the surgical treatments of pathological fractures in a series of patients treated in our institution who were affected by pycnodysostosis. Methods: We retrospectively evaluated clinical and radiographic characteristics of five patients with pycnodysostosis treated for pathological fractures at our hospital in the past 5 years. Results: Two male and three female patients were included in this study. Four patients had a family history of pycnodysostosis. All the patients were of short stature, but only two underwent growth hormone treatment. All the patients experienced fractures, mostly in their lower limbs and occurring as a result of low-energy trauma. Most of the patients experienced either consolidation delay or nonunion. Conclusions: The orthopedic management of fractures in patients with pycnodysostosis poses an ongoing challenge for orthopedic surgeons. The fact that the bone is simultaneously sclerotic and brittle makes any orthopedic surgical treatment challenging and at a high risk of nonunion in any case.