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Surgical treatment of scoliosis
Abstracts / Bone 45 (2009) S46–S52
P4 BMP Abstract to follow doi:10.1016/j.bone.2009.04.006
P5 Growth hormone—anabolic bone effects? Wolfgang Högler Department of Endocrinology and Diabetes, Birmingham Children’s Hospital, UK University of Birmingham, UK Growth hormone (GH) causes bone elongation during childhood and adolescence by stimulation of the growth plates but it is less known what it does to growth in bone width and strength (periosteal expansion). Recent studies in animals and humans with rare disorders of the GH axis have greatly contributed to our understanding of the paracrine and systemic effects of IgF-1 on bone structure. Bone elongation and periosteal expansion naturally go hand-in-hand to adapt bones to the increasing habitual forces during growth. In children with isolated GH deficiency (GHD), it is reasonable to assume that both processes should be equally compromised, leading to a proportionally smaller child with shorter, and proportionally narrower bones that should be well adapted to the lower habitual forces. There is no evidence that isolated childhood-onset GHD, or severe GH resistance, causes fractures in untreated children or adults. Periosteal expansion and bone geometry are a function of the forces acting on bones, which are mostly exerted by muscle pull, itself being heavily influenced by GH’s anabolic effect. In fact, muscle size in GHD children is lowest and increases most during GH therapy compared to any bone-related variable. According to the mechanostat theory, any structural bone measurements in GHD children, or any GH-treatment effects need to be interpreted relative to bone length and, if possible, to muscle size. Under this scrutiny, the short- and long-term effects of GH therapy on bone structure in childhood-onset GHD are minimal and probably secondary to GH-induced muscle enlargement. Also, dual-energy X-ray absorptiometry (DXA)-based studies are biased in individuals shorter (or taller) than average and corrections for size and/or muscle are a necessity. Since there is no increased fracture risk in isolated GHD, in contrast to hypopituitarism, DXA scanning is unnecessary, transition guidelines need updating and patients and parents should be protected from unnecessary anxiety. doi:10.1016/j.bone.2009.04.007
P6 Parathyroid hormone as a therapeutic agent Jeremy Allgrove Barts and the London NHS Trust, UK Parathyroid hormone (PTH) is an 84 amino acid polypeptide that has both anabolic and catabolic actions on bone. In physiological concentrations it promotes bone accretion whilst, at times of hypocalcaemic stress, it promotes bone resorption by increasing osteoclast activity. Hypoparathyroidism results in hypocalcaemia if untreated and bone loss may be significant. As a therapeutic agent PTH is available either as intact human sequence (1–84) hormone or as PTH (1–34), teriparatide, which exhibits full PTH activity. Both are licensed for the treatment of postmenopausal osteoporosis. Teriparatide is also licensed for use in
S47
men with osteoporosis and for corticosteroid-induced osteoporosis. Their use as therapeutic agents has been limited to these indications and neither has a license for use in children. There have been concerns about the possibility of patients developing bone tumours with prolonged use since rats given high doses of teriparatide showed an increased incidence of osteosarcoma. Nevertheless, it has been used in a few paediatric patients for the treatment of various forms of hypoparathyroidism that was not effectively controlled by vitamin D analogues, particularly those associated with activating mutations of the calcium sensing receptor (CaSR). In this condition inappropriate activation of the CaSR usually shifts the curve of response to plasma calcium to the left thereby inhibiting normal PTH secretion at lower calcium concentrations than normal. Despite this, urinary calcium excretion is elevated and made worse by treatment with vitamin D analogues. Occasionally the mutations cause constitutive activation of the receptor that prevents PTH secretion under any circumstances. This paper will briefly review the physiological actions of PTH and discuss current usage, both licensed and unlicensed, as a therapeutic agent. The use of synthetic PTH in children and the prospects for its use in the future will also be discussed. doi:10.1016/j.bone.2009.04.008
P7 Surgical treatment of scoliosis Hilali Noordeen Abstract to follow doi:10.1016/j.bone.2009.04.009
P8 Legg–Calve–Perthes disease and AVN Harry K.W. Kim Texas Scottish Rite Hospital for Children, USA Legg–Calve–Perthes disease is a juvenile form of osteonecrosis of the femoral head that affects children between the ages of 2 to 14 years. It remains one of the most controversial conditions in pediatric orthopaedics due to uncertainties regarding its etiology, natural history, pathogenesis, and management. The major problem associated with Perthes disease is the permanent femoral head deformity that can develop during the course of the disease and subsequent early osteoarthritis. A recent clinical study showed that a majority of children with early-onset disease (before age 6) had a good outcome (spherical femoral head) regardless of treatment received. However, in children with late-onset disease (after age 8), early surgical treatment group (femoral or pelvic osteotomy) had a better outcome than the non-surgical treatment group. Even with early surgical treatment, however, only 38–58% of the patients had a good outcome. These results indicate that current treatments do not directly address the pathobiology of the disease. Pathological remodeling of the necrotic bone marked by predominance of bone resorption and delayed new bone formation, producing a net bone loss, has been shown to contribute to the development of femoral head deformity in animal studies. Mechanical studies using a large animal model also demonstrated a significant compromise in the mechanical properties of the immature femoral head following the induction of osteonecrosis. New strategies to preserve the femoral head using antiresorptive and bone anabolic agents are being investigated. The results of anti-resorptive therapy using bisphosphonates and RANKL inhibitor on animal models appear promising. Clinical data on the
P4 BMP Abstract to follow doi:10.1016/j.bone.2009.04.006
P5 Growth hormone—anabolic bone effects? Wolfgang Högler Department of Endocrinology and Diabetes, Birmingham Children’s Hospital, UK University of Birmingham, UK Growth hormone (GH) causes bone elongation during childhood and adolescence by stimulation of the growth plates but it is less known what it does to growth in bone width and strength (periosteal expansion). Recent studies in animals and humans with rare disorders of the GH axis have greatly contributed to our understanding of the paracrine and systemic effects of IgF-1 on bone structure. Bone elongation and periosteal expansion naturally go hand-in-hand to adapt bones to the increasing habitual forces during growth. In children with isolated GH deficiency (GHD), it is reasonable to assume that both processes should be equally compromised, leading to a proportionally smaller child with shorter, and proportionally narrower bones that should be well adapted to the lower habitual forces. There is no evidence that isolated childhood-onset GHD, or severe GH resistance, causes fractures in untreated children or adults. Periosteal expansion and bone geometry are a function of the forces acting on bones, which are mostly exerted by muscle pull, itself being heavily influenced by GH’s anabolic effect. In fact, muscle size in GHD children is lowest and increases most during GH therapy compared to any bone-related variable. According to the mechanostat theory, any structural bone measurements in GHD children, or any GH-treatment effects need to be interpreted relative to bone length and, if possible, to muscle size. Under this scrutiny, the short- and long-term effects of GH therapy on bone structure in childhood-onset GHD are minimal and probably secondary to GH-induced muscle enlargement. Also, dual-energy X-ray absorptiometry (DXA)-based studies are biased in individuals shorter (or taller) than average and corrections for size and/or muscle are a necessity. Since there is no increased fracture risk in isolated GHD, in contrast to hypopituitarism, DXA scanning is unnecessary, transition guidelines need updating and patients and parents should be protected from unnecessary anxiety. doi:10.1016/j.bone.2009.04.007
P6 Parathyroid hormone as a therapeutic agent Jeremy Allgrove Barts and the London NHS Trust, UK Parathyroid hormone (PTH) is an 84 amino acid polypeptide that has both anabolic and catabolic actions on bone. In physiological concentrations it promotes bone accretion whilst, at times of hypocalcaemic stress, it promotes bone resorption by increasing osteoclast activity. Hypoparathyroidism results in hypocalcaemia if untreated and bone loss may be significant. As a therapeutic agent PTH is available either as intact human sequence (1–84) hormone or as PTH (1–34), teriparatide, which exhibits full PTH activity. Both are licensed for the treatment of postmenopausal osteoporosis. Teriparatide is also licensed for use in
S47
men with osteoporosis and for corticosteroid-induced osteoporosis. Their use as therapeutic agents has been limited to these indications and neither has a license for use in children. There have been concerns about the possibility of patients developing bone tumours with prolonged use since rats given high doses of teriparatide showed an increased incidence of osteosarcoma. Nevertheless, it has been used in a few paediatric patients for the treatment of various forms of hypoparathyroidism that was not effectively controlled by vitamin D analogues, particularly those associated with activating mutations of the calcium sensing receptor (CaSR). In this condition inappropriate activation of the CaSR usually shifts the curve of response to plasma calcium to the left thereby inhibiting normal PTH secretion at lower calcium concentrations than normal. Despite this, urinary calcium excretion is elevated and made worse by treatment with vitamin D analogues. Occasionally the mutations cause constitutive activation of the receptor that prevents PTH secretion under any circumstances. This paper will briefly review the physiological actions of PTH and discuss current usage, both licensed and unlicensed, as a therapeutic agent. The use of synthetic PTH in children and the prospects for its use in the future will also be discussed. doi:10.1016/j.bone.2009.04.008
P7 Surgical treatment of scoliosis Hilali Noordeen Abstract to follow doi:10.1016/j.bone.2009.04.009
P8 Legg–Calve–Perthes disease and AVN Harry K.W. Kim Texas Scottish Rite Hospital for Children, USA Legg–Calve–Perthes disease is a juvenile form of osteonecrosis of the femoral head that affects children between the ages of 2 to 14 years. It remains one of the most controversial conditions in pediatric orthopaedics due to uncertainties regarding its etiology, natural history, pathogenesis, and management. The major problem associated with Perthes disease is the permanent femoral head deformity that can develop during the course of the disease and subsequent early osteoarthritis. A recent clinical study showed that a majority of children with early-onset disease (before age 6) had a good outcome (spherical femoral head) regardless of treatment received. However, in children with late-onset disease (after age 8), early surgical treatment group (femoral or pelvic osteotomy) had a better outcome than the non-surgical treatment group. Even with early surgical treatment, however, only 38–58% of the patients had a good outcome. These results indicate that current treatments do not directly address the pathobiology of the disease. Pathological remodeling of the necrotic bone marked by predominance of bone resorption and delayed new bone formation, producing a net bone loss, has been shown to contribute to the development of femoral head deformity in animal studies. Mechanical studies using a large animal model also demonstrated a significant compromise in the mechanical properties of the immature femoral head following the induction of osteonecrosis. New strategies to preserve the femoral head using antiresorptive and bone anabolic agents are being investigated. The results of anti-resorptive therapy using bisphosphonates and RANKL inhibitor on animal models appear promising. Clinical data on the