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Bone strength in boys with Duchenne Muscular Dystrophy (DMD): A longitudinal study
Abstracts / Bone 45 (2009) S59–S111 No Fx Group AMB DMD LDF AMB DMD LS Non AMB DMD LDF Non AMB DMD LS Non AMB CP LDF Non ABM CP LS
n 19 19 13 7 28 16
Fx Z (R1, R2, R3) − 1.3, − 0.9, −0.6 Z = − 1.3 − 4.2, − 4.7, −4.8 Z = − 1.5 − 4.0, − 3.8, − 3.7 Z = − 2.8
n 4 3 13 8 19 8
Z (R1, R2, R3) − 2.1, −1.6, − 1.3 Z = − 2.4 − 4.2, − 4.6, − 4.8 Z = − 2.4 − 4.5, − 4.3, − 4.4 Z = − 3.4
Positive fracture history in ambulatory DMD was 4/23 with half occurring in the lower extremity. Non-ambulatory DMD fracture history was positive in 13/26 (with 69% in the lower extremity). Fracture history was positive in 19/47 of the CP group (lower extremity 89%). Both non-ambulatory groups had mean LDF Z-scores well below normal regardless of fracture history, whereas ambulatory DMD subjects had LDF values in normal/low-normal range. Ambulatory status did not influence LS Z-scores of DMD patients compared to LDF Z-scores. Differences in LDF Z-scores were noted in fracture and nonfracture groups except for the non-ambulatory DMD group. LDF BMD is easily obtained on disabled children and provides another DXA parameter for use in evaluating fracture risk. doi:10.1016/j.bone.2009.04.100
PW-58 Bone strength in boys with Duchenne Muscular Dystrophy (DMD): A longitudinal study N.J. Crabtreea,b, K.A. Wardc, H. Roperd, J.E. Adamsc, M.Z. Mughale, N.J. Shawb a University Hospital Birmingham, Birmingham, UK b Birmingham Children's Hospital, Birmingham, UK c ISBE, The University, Manchester, UK d Heartlands Hospital, Birmingham, UK e St. Mary's Hospital for Women and Children, Manchester, UK DMD is the most common childhood neuromuscular disorder causing loss of ambulation in early life. Steroids are currently used to improve muscle strength and prolong ambulation although the effect on bone health in this group of children is still unclear. The aim of this study was to compare the longitudinal changes in bone strength in healthy children with those observed in children with DMD, who either remained ambulant or who lost independent ambulation during the period of follow-up. Forty children were studied, 17 healthy boys (9.1 ± 1.5 years) and 23 boys with DMD (8.6 ± 2.1 years), taking intermittent steroids. PQCT was used to measure bone geometry, density and strength of the non-dominant tibia. Measurements were made at the distal metaphysis and mid-diaphysis sites. Data were adjusted for age, height and duration of steroids. After 15.0 ± 3.1 months, 7 DMD boys lost independent ambulation. Longitudinal growth between the groups remained constant. In DMD boys, who remained ambulant, there was a slowing down in periosteal bone growth at the mid diaphysis (0.8 vs. 2.6 mm2/month; p < 0.05). Whereas for DMD boys who lost ambulation, there was a significant reduction in the rate of bone growth at the mid-diaphysis (0.4 mm2/month; p < 0.05) and at the distal metaphysis (2.8 vs. 6.2 mm2/month; p < 0.05). In contrast, the rate of change in bone density at the distal metaphysis (− 2.8 vs. 0.3 mg/cm3/month; p < 0.001) and cortical bone mass (− 0.2 vs. 1.3 mg/mm/month; p < 0.001) and stress-strain index (2.0 vs. 9.9 mm3/month; p < 0.05) at the mid diaphysis was only significantly different from the healthy boys in the 7 boys who lost independent ambulation. These data suggest that ambulation and hence muscle function and gravitational load have the greatest effect on bone strength and
S79
density in boys with DMD. Whilst they remain ambulant the effect of the relatively high dose steroids appears to be negligible. However, when they eventually lose independent ambulation significant losses in bone strength occur as a direct result of diminished periosteal bone growth and bone mineral accrual. doi:10.1016/j.bone.2009.04.101
PW-59 The effect of hypogonadism and growth hormone deficiency on bone microarchitecture in thalassemia major patients R. Grossea, I. Frielingb, A. Wuesthofc, E. Fungd, R. Fischera,d, R. Schneppenheima, G. Jankaa a University Hospital Hamburg-Eppendorf, Hamburg, Germany b Osteoporosis Center Hamburg, Hamburg, Germany c Endocrinologikum Hamburg, Hamburg, Germany d Childrens Hospital Oakland, Oakland, USA In recent decades, survival in thalassemia major patients has dramatically improved. However, complications such as osteopenia and osteoporosis are still prevalent in nearly 70% of these patients. This leads to significant morbidity including fractures, bone pain and decreased quality of life. The diagnosis of osteoporosis is typically made by endocrine assessment and 2-dimensional bone mineral density (BMD) measurements like dual energy x-ray absorptiometry (DXA), which may be insufficient. In addition to planar BMD by DXA and endocrine parameters, we assessed the bone microarchitecture and the volumetric BMD of the non-dominant distal radius and tibia by high-resolution peripheral quantitative computed tomography (HRpQCT: XtremeCT®, SCANCO Medical AG). In 18 transfused patients (age: 13–43 years, 9/18 female) with thalassemia major, BMD of the lumbar spine (LS) and total hip was measured by DXA resulting in 7/ 18 patients with calculated Z-scores < −2.0. The SD of the trabecular separation (TbSp SD) by HR-pQCT of radius and tibia, characterizing the porosity of the spongiosa, may become the most interesting parameter in thalassemia as it was significantly correlated with age (RS = 0.79, p = 0.0001), hip Z-score (RS = − 0.49, p = 0.044), osteocalcin (RS = −0.70, p = 0.001), FSH (RS = − 0.65, p = 0.005), IgF-1 (RS = −0.58, p = 0.007) and with liver iron concentration (tibia: RS = 0.55, p = 0.017), respectively. Patients with fractures (n = 5) had lower total densities (p = 0.02) and tibial TbSp SD (p = 0.02). Patients with hypogonadism (n = 9/ 18, FSH: 0.1–1.7 U/l) were significantly different (U-test) from normals (FSH: 2.1–6.8 U/l) with respect to TbSp SD (p = 0.019), but not for DXA Z-scores. Many patients with thalassemia are affected by hypogonadism and growth hormone deficiency. For these patients, the measurement of bone microarchitecture by HR-pQCT of low radiation burden (3 μSv) may help to identify fracture risk early. Growth hormone (GH) and IGF-I, which only correlated with HR-pQCT but not with DXA, are especially important regulators of bone homeostasis and are central to the achievement of normal bone growth and peak bone mass. doi:10.1016/j.bone.2009.04.102
PW-60 Association of physeal growth arrest and limb amputation following meningococcal septicaemia in children H. Akrawi, M. Uglow Southampton University Hospitals NHS Trust, Southampton, Hampshire, UK
n 19 19 13 7 28 16
Fx Z (R1, R2, R3) − 1.3, − 0.9, −0.6 Z = − 1.3 − 4.2, − 4.7, −4.8 Z = − 1.5 − 4.0, − 3.8, − 3.7 Z = − 2.8
n 4 3 13 8 19 8
Z (R1, R2, R3) − 2.1, −1.6, − 1.3 Z = − 2.4 − 4.2, − 4.6, − 4.8 Z = − 2.4 − 4.5, − 4.3, − 4.4 Z = − 3.4
Positive fracture history in ambulatory DMD was 4/23 with half occurring in the lower extremity. Non-ambulatory DMD fracture history was positive in 13/26 (with 69% in the lower extremity). Fracture history was positive in 19/47 of the CP group (lower extremity 89%). Both non-ambulatory groups had mean LDF Z-scores well below normal regardless of fracture history, whereas ambulatory DMD subjects had LDF values in normal/low-normal range. Ambulatory status did not influence LS Z-scores of DMD patients compared to LDF Z-scores. Differences in LDF Z-scores were noted in fracture and nonfracture groups except for the non-ambulatory DMD group. LDF BMD is easily obtained on disabled children and provides another DXA parameter for use in evaluating fracture risk. doi:10.1016/j.bone.2009.04.100
PW-58 Bone strength in boys with Duchenne Muscular Dystrophy (DMD): A longitudinal study N.J. Crabtreea,b, K.A. Wardc, H. Roperd, J.E. Adamsc, M.Z. Mughale, N.J. Shawb a University Hospital Birmingham, Birmingham, UK b Birmingham Children's Hospital, Birmingham, UK c ISBE, The University, Manchester, UK d Heartlands Hospital, Birmingham, UK e St. Mary's Hospital for Women and Children, Manchester, UK DMD is the most common childhood neuromuscular disorder causing loss of ambulation in early life. Steroids are currently used to improve muscle strength and prolong ambulation although the effect on bone health in this group of children is still unclear. The aim of this study was to compare the longitudinal changes in bone strength in healthy children with those observed in children with DMD, who either remained ambulant or who lost independent ambulation during the period of follow-up. Forty children were studied, 17 healthy boys (9.1 ± 1.5 years) and 23 boys with DMD (8.6 ± 2.1 years), taking intermittent steroids. PQCT was used to measure bone geometry, density and strength of the non-dominant tibia. Measurements were made at the distal metaphysis and mid-diaphysis sites. Data were adjusted for age, height and duration of steroids. After 15.0 ± 3.1 months, 7 DMD boys lost independent ambulation. Longitudinal growth between the groups remained constant. In DMD boys, who remained ambulant, there was a slowing down in periosteal bone growth at the mid diaphysis (0.8 vs. 2.6 mm2/month; p < 0.05). Whereas for DMD boys who lost ambulation, there was a significant reduction in the rate of bone growth at the mid-diaphysis (0.4 mm2/month; p < 0.05) and at the distal metaphysis (2.8 vs. 6.2 mm2/month; p < 0.05). In contrast, the rate of change in bone density at the distal metaphysis (− 2.8 vs. 0.3 mg/cm3/month; p < 0.001) and cortical bone mass (− 0.2 vs. 1.3 mg/mm/month; p < 0.001) and stress-strain index (2.0 vs. 9.9 mm3/month; p < 0.05) at the mid diaphysis was only significantly different from the healthy boys in the 7 boys who lost independent ambulation. These data suggest that ambulation and hence muscle function and gravitational load have the greatest effect on bone strength and
S79
density in boys with DMD. Whilst they remain ambulant the effect of the relatively high dose steroids appears to be negligible. However, when they eventually lose independent ambulation significant losses in bone strength occur as a direct result of diminished periosteal bone growth and bone mineral accrual. doi:10.1016/j.bone.2009.04.101
PW-59 The effect of hypogonadism and growth hormone deficiency on bone microarchitecture in thalassemia major patients R. Grossea, I. Frielingb, A. Wuesthofc, E. Fungd, R. Fischera,d, R. Schneppenheima, G. Jankaa a University Hospital Hamburg-Eppendorf, Hamburg, Germany b Osteoporosis Center Hamburg, Hamburg, Germany c Endocrinologikum Hamburg, Hamburg, Germany d Childrens Hospital Oakland, Oakland, USA In recent decades, survival in thalassemia major patients has dramatically improved. However, complications such as osteopenia and osteoporosis are still prevalent in nearly 70% of these patients. This leads to significant morbidity including fractures, bone pain and decreased quality of life. The diagnosis of osteoporosis is typically made by endocrine assessment and 2-dimensional bone mineral density (BMD) measurements like dual energy x-ray absorptiometry (DXA), which may be insufficient. In addition to planar BMD by DXA and endocrine parameters, we assessed the bone microarchitecture and the volumetric BMD of the non-dominant distal radius and tibia by high-resolution peripheral quantitative computed tomography (HRpQCT: XtremeCT®, SCANCO Medical AG). In 18 transfused patients (age: 13–43 years, 9/18 female) with thalassemia major, BMD of the lumbar spine (LS) and total hip was measured by DXA resulting in 7/ 18 patients with calculated Z-scores < −2.0. The SD of the trabecular separation (TbSp SD) by HR-pQCT of radius and tibia, characterizing the porosity of the spongiosa, may become the most interesting parameter in thalassemia as it was significantly correlated with age (RS = 0.79, p = 0.0001), hip Z-score (RS = − 0.49, p = 0.044), osteocalcin (RS = −0.70, p = 0.001), FSH (RS = − 0.65, p = 0.005), IgF-1 (RS = −0.58, p = 0.007) and with liver iron concentration (tibia: RS = 0.55, p = 0.017), respectively. Patients with fractures (n = 5) had lower total densities (p = 0.02) and tibial TbSp SD (p = 0.02). Patients with hypogonadism (n = 9/ 18, FSH: 0.1–1.7 U/l) were significantly different (U-test) from normals (FSH: 2.1–6.8 U/l) with respect to TbSp SD (p = 0.019), but not for DXA Z-scores. Many patients with thalassemia are affected by hypogonadism and growth hormone deficiency. For these patients, the measurement of bone microarchitecture by HR-pQCT of low radiation burden (3 μSv) may help to identify fracture risk early. Growth hormone (GH) and IGF-I, which only correlated with HR-pQCT but not with DXA, are especially important regulators of bone homeostasis and are central to the achievement of normal bone growth and peak bone mass. doi:10.1016/j.bone.2009.04.102
PW-60 Association of physeal growth arrest and limb amputation following meningococcal septicaemia in children H. Akrawi, M. Uglow Southampton University Hospitals NHS Trust, Southampton, Hampshire, UK