Aims. The prevalence of scoliosis is not known in patients with idiopathic short stature, and the impact of treatment with recombinant human growth hormone on those with scoliosis remains controversial. We investigated the prevalence of scoliosis radiologically in children with idiopathic short stature, and the impact of treatment with growth hormone in a cross-sectional and retrospective cohort study. Methods. A total of 2,053 children with idiopathic short stature and 4,106 age- and sex-matched (1:2) children without short stature with available whole-spine radiographs were enrolled in the cross-sectional study. Among them, 1,056 with idiopathic short stature and 790 controls who had radiographs more than twice were recruited to assess the development and progression of scoliosis, and the need for bracing and surgery. Results. In the cross-sectional study, there was an unexpectedly higher prevalence of scoliosis (33.1% (681/2,053) vs 8.52% (350/4,106)) in children with idiopathic short stature compared with controls (odds ratio 3.722; p < 0.001), although most cases were mild. In the longitudinal study, children with idiopathic short stature had a higher risk of the development and progression of scoliosis than the controls. Among children with idiopathic short stature without scoliosis at baseline, treatment with growth hormone significantly increased the risk of developing scoliosis (p = 0.015) and the need for bracing (p < 0.001). Among those with idiopathic short stature and scoliosis at baseline, treatment with growth hormone did not increase the risk of progression of the scoliosis, the need for bracing, or surgery. Conclusion. The impact of treatment with growth hormone on scoliosis in children with idiopathic short stature was considered controllable. However, physicians should pay close attention to the assessment of spinal curves in these children. Cite this article: Bone Joint J 2023;105-B(4):439–448

Introduction: Following an Australian study on the incidence of scoliosis in a population of short-statured children treated with human growth hormone (conducted during 2001–2002), it was determined that the only risk factor for the presence of idiopathic scoliosis was having Turner/another syndrome. The 30% incidence in Turner syndrome was noted to be much higher than previously reported (11–12%). The aim of this study is to determine the incidence of scoliosis in a group of growth hormone-treated and non-treated Turner Syndrome subjects who attended the International Turner Syndrome Society meeting in Sydney, Australia in July 2003 and to correlate the results with the Australian 2001–2002 results. Methods: 88 subjects were clinically examined for the presence and severity of idiopathic scoliosis. Their ages ranged from 11 to 60 years. All subjects provided information regarding previous growth hormone and/or oestrogen administration. Anthropometric data including sitting and standing height and arm span was also collated on this cohort. Results: 13 of 46 (28.3%) subjects who had no growth hormone treatment were found to have scoliosis. Five of 42 (12%) subjects who were growth hormone treated were found to have scoliosis. 12 curves were thoracic, five were thoracolumbar and one was lumbar. The 13 subjects with scoliosis and no growth hormone treatment had curves between10 and 20° Cobb angle. Three growth hormone-treated subjects had curves of 10°, one had a curve of 30° and the last subject had already undergone scoliosis surgery. Combining the results of this study with the three Australian States study from 2001–2002, 18 of 87 (21%) growth hormone-treated Turner syndrome subjects have idiopathic scoliosis. 13 of 46 (28%) non-growth hormone-treated Turner syndrome subjects also have idiopathic scoliosis. Of the total 133 subjects in this cohort, 31 (23%) have idiopathic scoliosis. Discussion: The incidence of idiopathic scoliosis in Turner syndrome appears to have been understated in previous studies. Data from this study would indicate that treating children who have Turner syndrome with adjuvant human growth hormone does not appear to result in a greater incidence or severity of idiopathic scoliosis. In this relatively small study, two of five children who had previous growth hormone treatment developed larger curves, one requiring corrective scoliosis surgery

Introduction: Retrospective reports of adverse events following growth hormone administration to short-statured children indicate that the incidence of scoliosis is elevated, largely due to the higher incidence of scoliosis in Turner/other syndromes within the group. The aims of this study are to analyse risk factors for scoliosis in these children. Methods: Data on 184 of 267 (65%) current and recent Australian children from the Australian OZGROW program was collected in 2001/2002 (from three Australian States). This included medical records (including past history of known scoliosis), growth charts, timing of growth hormone and oestrogen administration and the presence and severity of scoliosis from clinical examination. Growth hormone dosage was controlled by Australian Health Department guidelines. Standard oestrogen dosage was similar for all pubertal girls. The cohort was noted to comprise many varying syndromes, some of whom were pituitary hormone deficient. Potential risk factors for the development of scoliosis were statistically analysed. Results: Of 45 subjects with Turner Syndrome, 13 (30%) have idiopathic scoliosis and 2 have a hemi-vertebra. Of the other 139 subjects, 15 have scoliosis but 11 have syndromes which would normally be associated with scoliosis. Therefore, the incidence of idiopathic scoliosis in the remaining 128 subjects is 3.1% (4/128), which is within the normal population range. All 4 have mild scoliosis < 20 degrees. For the 139 subjects with idiopathic short stature or a specific syndrome, the age of commencement and total amount of growth hormone and/or oestrogen did not affect the degree of scoliosis. Discussion: Having Turner Syndrome was the only variable identified as a risk factor for having scoliosis (p< .001). The incidence of scoliosis in growth hormone treated Turner Syndrome subjects is much larger than previously reported (11–12%). 1,. 2. To the authors’ knowledge, this is the first report derived from non-retrospective data on the incidence of scoliosis in a growth hormone–treated Turner Syndrome population. This stimulated the next study looking at the incidence of scoliosis in growth hormone-treated and non-growth hormone-treated subjects with Turner Syndrome

In 65 mature Wistar rats a Kirschner wire was introduced into the medullary cavity of each femur. A closed transverse mid-shaft fracture of one femur was produced by a three-point bending technique. Subsequently the mechanical characteristics of the healing fracture, including the torque and angle of twist required to take the callus to its yield point and to ultimate failure, were compared with those for the opposite femur of each rat. Controls were killed in groups at two, three, four, five and seven weeks. Test animals were given bovine growth hormone in a daily dose of five milligrams before being killed in groups at two, three and four weeks. A significant increase in torque index was found in the two-week group of test animals but not in subsequent groups. No evidence was found that growth hormone given alone could produce an overall shortening of the healing time in fresh fractures

1. A case is reported of a girl aged fifteen with growth hormone deficiency who developed a slip of the left femoral capital epiphysis at the age of seventeen during human growth hormone therapy. 2. The epiphysiolysis is regarded as iatrogenic

A one-year-8-month-old girl who received radiotherapy and chemotheraphy after excision of embryonal rhabdomyosarcoma from left labium majus pudendi developed slipped capital femoral epiphysis (SCFE) over right hip when she was 9 years old. After mild limp had been noted for 6 months she was then referred to pediatric orthopedic surgeon and two Knowles pins were used to fix the slipping. The second case was a 17-year-old girl with Turner syndrome. SCFE developed during the growth hormone therapy and it was treated with percutaneous pinning with two cannnulated screws. The possibility of developing SCFE should always be kept in mind when treating and following these particular cases to avoid delay of diagnosis

Aims. The assessment of the potential pathological influence of Growth Hormone (hGH), Testosterone, Estradiol, Follicle Stimulating Hormone (FSH) and Luteinizing Hormone in the development of SCFE and the re-evaluation of the Harris theory (increased quotient of hGH/sex hormones in patients suffering from SCFE). Methods. Nineteen patients in total were included in the study. Fourteen patients (7 boys, 7 girls, 16 hips) suffering from SCFE during the proceeding of this study, formed group ‘A’. Another 5 patients (4 boys, 1 girl), that had been treated for SCFE a few years before the study, formed group ‘B’. We measured serum hGH, FSH, LH, Testosterone and Estradiol levels. Furthermore we checked all necessary anthropometrical and clinical characteristics (age, height & weight, sexual maturation, grade of slipping). Results. Thirty six out of 95 in total measurements (37,9%) revealed pathological values. The majority of group A patients had pathological values (43% of measurements). The Harris theory seems to be true in 7 out of 19 in total patients: 5 group A patients (2 boys and 3 girls) and 2 group B patients (1 boy and 1 girl). Conclusions. We believe that a temporary (?) disorder or imbalance of hGH and sexhormones, under the possible influence of FSH and LH (along with other etiologic factors) during the early years of adolescence, may play a potentially significant role in the development of SCFE

The April 2024 Research Roundup. 360. looks at: Prevalence and characteristics of benign cartilaginous tumours of the shoulder joint; Is total-body MRI useful as a screening tool to rule out malignant progression in patients with multiple osteochondromas?; Effects of vancomycin and tobramycin on compressive and tensile strengths of antibiotic bone cement: a biomechanical study; Biomarkers for early detection of Charcot arthropathy; Strong association between growth hormone therapy and proximal tibial physeal avulsion fractures in children and adolescents; UK pregnancy in orthopaedics (UK-POP): a cross-sectional study of UK female trauma and orthopaedic surgeons and their experiences of pregnancy; Does preoperative weight loss change the risk of adverse outcomes in total knee arthroplasty by initial BMI classification?

Aims. Osteoarthritis (OA) is the most prevalent systemic musculoskeletal disorder, characterized by articular cartilage degeneration and subchondral bone (SCB) sclerosis. Here, we sought to examine the contribution of accelerated growth to OA development using a murine model of excessive longitudinal growth. Suppressor of cytokine signalling 2 (SOCS2) is a negative regulator of growth hormone (GH) signalling, thus mice deficient in SOCS2 (Socs2. -/-. ) display accelerated bone growth. Methods. We examined vulnerability of Socs2. -/-. mice to OA following surgical induction of disease (destabilization of the medial meniscus (DMM)), and with ageing, by histology and micro-CT. Results. We observed a significant increase in mean number (wild-type (WT) DMM: 532 (SD 56); WT sham: 495 (SD 45); knockout (KO) DMM: 169 (SD 49); KO sham: 187 (SD 56); p < 0.001) and density (WT DMM: 2.2 (SD 0.9); WT sham: 1.2 (SD 0.5); KO DMM: 13.0 (SD 0.5); KO sham: 14.4 (SD 0.7)) of growth plate bridges in Socs2. -/-. in comparison with WT. Histological examination of WT and Socs2. -/-. knees revealed articular cartilage damage with DMM in comparison to sham. Articular cartilage lesion severity scores (mean and maximum) were similar in WT and Socs2. -/-. mice with either DMM, or with ageing. Micro-CT analysis revealed significant decreases in SCB thickness, epiphyseal trabecular number, and thickness in the medial compartment of Socs2. -/-. , in comparison with WT (p < 0.001). DMM had no effect on the SCB thickness in comparison with sham in either genotype. Conclusion. Together, these data suggest that enhanced GH signalling through SOCS2 deletion accelerates growth plate fusion, however this has no effect on OA vulnerability in this model. Cite this article: Bone Joint Res 2022;11(3):162–170

Introduction and Aims: SHOX haploinsufficiency presents with Turner syndrome dysmorphic skeletal features – micrognathia (60%), cubitus valgus (47%), high-arched palate (25%) and Madelung deformity (7%). Idiopathic scoliosis is also present in 11% of Turner syndrome. This clinical observation and radiological study explores the possibility of SHOX haploinsufficiency expression in the scoliotic spine in Turner syndrome. Method: Turner syndrome presents a mesomelic short stature, thought to result from growth plate dysmorphism, presumably from SHOX gene haploinsufficiency. Forty-five Turner syndrome subjects on the Australian Growth Hormone program were clinically examined for the presence of idiopathic scoliosis. Of another 88 Turner syndrome subjects similarly examined, 46 had received growth hormone and 42 had never received growth hormone. Kosowicz (1959) and Preger (1968) noted irregular vertebral endplates of scoliotic spines in Turner syndrome subjects. This may imply dysmorphic vertebral growth plates. A spinal MRI and plain imaging study of idiopathic scoliosis with/without Turner syndrome was undertaken to examine for vertebral growth plate abnormalities. Results: This study again demonstrates plain radiographic presence of irregular vertebral endplates of scoliotic spines in Turner syndrome. Spine MR imaging in Turner syndrome failed to clearly demonstrate the growth plates but demonstrated wedge-shaped distal vertebrae in the curve. Similar MR findings were noted in another 20 subjects with various causes of scoliosis. Wedged-shaped intervertebral discs were also noted, but are thought to be secondary changes. Of 87 Turner syndrome subjects from growth hormone programs, 18 (21%) were found to have idiopathic scoliosis. Thirteen of another 46 (28%) subjects who had never received growth hormone were also noted to have idiopathic scoliosis, indicating a combined incidence of 23%. These results contrast with Lippe (1991) and Kim (2001), who noted an incidence of 11% of 163 and 12% of 43 idiopathic scoliosis in Turner syndrome from retrospective observation. However, the incidence of scoliosis (41%) from the radiographic studies of Kosowicz (4/22) and Preger (19/34) is much greater than even the incidence noted clinically from this study. Conclusion: SHOX haploinsufficiency expression is not yet described in Turner syndrome scoliotic spines, although it has been described in the distal radius (Munns, 2001) in Madelung deformity. The incidence of idiopathic scoliosis in Turner syndrome appears to be much larger than previously recognised, signalling a probable dysmorphic vertebral growth plate cause

Purpose of the study: Determine the prevalence and course of spinal deformations in Willi-Prader syndrome and assess the effect of treatment with growth hormone. Analyze outcome after conservative and surgical treatments. Material and methods: We reviewed the files of 51 patients with Willi-Prader syndrome proven genetically. Spinal deformations were classed according to the SRS system. Body mass index (BMI) was determined and correlated with age and administration of growth hormone. Statistical analysis used the coefficient of correlation and the chi-square test to search for correlations between qualitative variables. Results: There were 37 girls and 24 boys, mean age at last follow-up 10.7±6.7 years. The prevalence of scoliosis was 52% and varied according to genotype. The prevalence of scoliosis deformations was higher in patients aged over ten years (p< 0.01). The prevalence of scoliosis was greater in female patients. Patients with BMI< 25 had a significantly lower risk of scoliosis. Treatment with growth hormone was associated with a significant decrease in risk of scoliosis. Among scoliosis patients, ten had a main curvature < 15° and were monitored. Eleven had a curvature > 15° (31±11°) and were treated with a corset. Five had a curvature > 50° and trunk imbalance and were treated surgically. Four of these patients developed serious complications. Discussion: Scoliosis deformation is frequent in Willi-Prader syndrome. Weight control is very important and BMI should be maintained below 25 to limit the risk of scoliosis. Treatment with growth hormone helps limit BMI and thus the risk of scoliosis. For major deformations, surgical treatment is indicated but at the risk of serious postoperative complications

Introduction Delayed puberty and delayed skeletal maturation have been implicated as risk factors for the progression of idiopathic scoliosis. Genetic defects (Turner syndrome) and hypothalamic- pituitary disorders are known causes of delayed puberty. Although it is recognized that the incidence of idiopathic scoliosis is elevated in Turner syndrome, human studies regarding the incidence/severity of scoliosis in children with suprasellar, hypothalamic region and pituitary tumours/ disorders is deficient. Methods A medical records search in five Australian states for suprasellar, hypothalamic region and pituitary tumours/disorders was performed. Identified patients underwent clinical or radiological evaluation for scoliosis. Pathology varied from suprasellar-hypothalamic region tumours, pan-hypopituitarism, pituitary tumours and growth hormone deficiency as well as a craniopharyngioma, arachnoid cyst, retinoblastoma and encephalocele. Results Of 23 identified patients, ten are female. Mean age at presentation was 8.4 years. Three have right thoracic scoliosis with a Cobb angle less than 20 degrees. Two are males; one with pituitary hormone deficiency and the other with Cushing’s disease treated with radiotherapy. The only female is on a growth hormone treatment program for idiopathic growth hormone deficiency. Discussion The only female with scoliosis was 12 years old. Delayed puberty could not be linked to either male with scoliosis. Although the incidence of idiopathic scoliosis in this cohort is greater than expected from Caucasian population studies (2–3%), the male preponderance is unusual. No relationship between delayed skeletal maturation and idiopathic scoliosis could be established

1. The clinical features of hyperostosis cranii are briefly reviewed. In large series of cases the syndrome has been found to occur almost entirely in females. 2. In recent studies of dystrophia myotonica, it is apparent that hyperostosis cranii is one of the variable features of the disorder. This disease occurs equally among males and females and the hyperostosis cranii also is distributed equally among males and females. 3. Hyperostosis cranii also occurs in patients with Morgagni's syndrome, with acromegaly, and as "senile hyperostosis.". 4. The etiology of hyperostosis is still a matter for speculation. More recent studies have focused attention on the endocrine system, and it seems probable, in view of the sex distribution in dystrophia myotonica, that the key to the problem may be found in this disorder. 5. In dystrophia myotonica the characteristic skull changes are hyperostosis cranii, a small pituitary fossa, excessive sinus formation and prognathism. These are acromegaloid changes. Gonadal atrophy is a common feature and endocrine study suggests that the endocrine defect is primarily a failure of the androgenic function of the adrenals and the testes. 6. In rodents and in humans ablation of the gonads leads to overactivity of gonadotrophic cells and, at times, of somatotrophic cells. Sometimes pituitary tumours develop. 7. Acromegaloid features may occur in eunuchs, and it is likely that the acromegaloid changes in dystrophia myotonica are of the same order from overactivity of growth hormone. 8. In animals excess of growth hormone produces thickening of the skull. 9. In dystrophia myotonica, acromegaly, and Morgagni's syndrome, it is suggested that hyperostosis cranii is an expression of unrestrained activity of growth hormone

Four cases of slipped upper femoral epiphyses in patients with intracranial tumours causing hypopituitarism and chiasmal compression are presented. Detailed endocrine studies in three cases showed severe deficiencies of growth hormone as well as of gonadotrophin and sex hormones. The literature is reviewed and the aetiology is discussed with special reference to Harris's hypothesis that an increase in growth hormone relative to oestrogen predisposes to slipping of the upper femoral epiphysis in humans, which these cases do not seem to support. In all cases the slip was bilateral, and it is emphasised that surgical treatment can provide only temporary fixation because fusion is dependent on correct hormonal therapy

Summary. Arginine supplementation is helpful in treatment of osteoporosis. Introduction. Nitric oxide (NO) is a short-lived free radical involved in several biological processes as a bioregulator and as a second messenger. It inhibits osteoclastic bone resorption in vitro and regulates bone remodeling. Zolendronic acid has been established as a treatment for post menopausal osteoporosis. Study was done to compare the efficacy of Nitic oxide donor (L-arginine) with that of Zolendronic acid for the treatment of osteoporosis. Method. The study was not designed to compare these two drugs against a placebo, because the beneficial effects of Zolendronic acid in treatment of osteoporosis are well established. Institutional Review Board approvals were obtained. One hundred patients of osteoporosis having T score of −2.5 or more, were randomised to receive L-arginine) or Zolendronic acid. All patients received 1.0 g of calcium and 400 IU of vitamin D supplementation per day. In addition Group I patients received L-arginine (2 gm.) per day while Group II patients received zoledronic acid 5 mg i.v. over 15 min. Patient were followed at regular intervals clinically, by biochemical investigations and at one year for DEXA scan. Results. Patients in both groups improved clinically and bio-chemically over one year period. T score on DEXA scan at one year showed improvement in bone density. Average pretreatment T score was −3.65 in group I and −3.52 in group II. At one year followup average T score was −2.9 in group I and −2.6 in group II. Difference was not statistically significant. Discussion. Oral administration of L-arginine in pharmacological doses induces growth hormone and insulin like growth factor-1 responses and stimulates nitric oxide synthesis. Growth hormone and insulin like growth factor-1 are important mediator of bone turnover and osteoblastic bone formation. While nitric oxide is potent inhibitor of osteoclastic bone resorption because of this dual effect on physiological regulator of bone remodeling. L-arginine could potentially increase bone formation over bone resorption and consequently increase bone mass. Oral supplementation of L-arginine may be novel strategy in prevention and treatment of osteoporosis

Background. Acromegaly, which stems from high level of serum growth hormone secreted by a benign tumour in the anterior pituitary gland, is likely to cause severe peripheral joint pains due to hypertrophic changes in such joints. Recently, the life expectancy of such patients has been improved and more patients with acromegaly have undergone joint surgeries to mitigate joint pain and malfunctions. However, little is known about to what extent surgical procedures can improve the joint functions of acromegalic patients compared to non-acromegalic cases. Methods. First, we qualitatively analysed prognosis of total hip arthroplasty (THA) of acromegalic patients by investigating 11 cases in which direct anterior approach (DAA) THAs were performed to 8 acromegalic patients in our hospital between 2012 and 2015. Second, we quantitatively compared the functional prognosis of the 11 cases with that of 107 non-acromegalic cases. Technically, to control the difference in age, sex, height, and weight between the two patient groups, we first identified a model that could predict 3month-/6month-/12month-functional prognosis in the control cases. We estimated differences in functional outcomes between the two groups by calculating how accurately the control-case-based model could predict the prognosis of the acromegalic cases. Results. In the qualitative analysis, we found that compared to the control, the most acromegalic cases had atypically advanced degenerative arthritides with osteophytes and enthesophytes proliferations. In addition, some cases showed other signs, such as flattering of femoral head and arthritis with slight osteophytes. Regarding surgical procedures, acromegalic cases were likely to require longer operation time and larger amounts of blood loss compared to the control. In the quantitative analysis, we first identified a model in which age and body height could predict the functional prognosis of DAA THA in the non-acromegalic cases (F[2,104] = 6.7, P = 0.0017). We then found that the actual functional outcomes of the acromegalic cases were not significantly different from those predicted by this control-case-based model (P = 0.18). Conclusions. The qualitative analysis shows the atypical joint structures and resultant prolonged operation time and blood loss in the acromegalic cases. However, the quantitative analysis could not find significant differences in prognosis between the acromegalic and non-acromegalic cases. Although these observations and analyses need to be examined in studies with large sample sizes, this work suggests that functional outcomes of DAA THA to acromegalic patients can be comparable to that to non-acromegalic patients

1. In growing rats oestrogen, cortisone and thyroxine in high doses suppress bone formation, and this effect is probably part of a general suppression of body growth. 2. Growth hormone and thyroxine in small doses stimulate both body growth and bone formation. 3. Testosterone has no effect on bone formation. 4. Oestrogen and cortisone suppress bone resorption. The effect of cortisone may be modified in conditions of calcium depletion. 5. Thyroxine appears on the other hand to increase bone resorption. 6. Testosterone has no effect on bone resorption

Two cases of bilateral slipping of the upper femoral epiphysis in boys with end-stage renal failure due to megacystis and mega-ureter with severe renal osteodystrophy are reported. In one patient the lesion emerged after a dystonic reaction to drugs and in the other after bilateral nephro-ureterectomy. Neither showed marked elevation of growth hormone levels, but both had evidence of renal rickets with severe secondary hyperparathyroidism. Both had a satisfactory response to bilateral internal fixation. The complication should be borne in mind in all young patients with renal osteodystrophy

In 15 consecutive patients with slipped capital femoral epiphysis we recorded height, weight and skeletal maturity. Sexual maturity was assessed clinically and biochemically, and Harris's hypothesis that there is an increased ratio of serum growth hormone to oestrogen was tested in comparison with 15 age and sex matched controls. We found no difference in skeletal or sexual maturity between the groups, or any overt endocrine abnormality in the patients. However almost half the patients with slipped epiphysis were over the 90th weight percentile, suggesting that mechanical factors such as obesity are more important aetiologically than endocrine abnormalities

Eight children developed osteochondroma (OS) at a mean of 88 months, after hematopoietic stem cell transplantation (HSCT). The mean age at HSCT was 56 months (12-84). This represents a cumulative incidence of 20% among patients less than 18 years of age transplanted from 1981 to 1997. These eight patients underwent allogeneic (n=2) of autologous (n=6) transplantation for either acute leukemia (n=6) or neuroblastoma (n=2) after a conditioning regimen including total body irradiation (n=7) or a combination of Busulfan and Cyclophosphamide.Multiple OS were indentified in seven patients and a solitary OS in one. Locations included: clavicle (2), ribs (2), superior iliac epiphysis (1), metaphy-sis of the distal femur (2), distal (2) and proximal (1) tibia, proximal humerus (1), distal radii (3), scapula (3), proximal metaphysis of the proximal phalanges of the fingers (2) and parietal bone (1). OS were asymptomatic in four children. Eight lesions in five patients were resected and all were benign. No recurrence occured.Four children received growth hormone before diagnosis of OS, but there was no clinical, radiological or histological difference between those who did not. Univariate analysis showed an increased rate associated only with autolo-gous HSCT, with a 31,7% probability of a new OS et 12 years after HSCT.Ostoechondroma should be added to the other adverse effects of HSCT in children