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Use of total body MRI for the diagnosis of multifocal ON lesions: Case report
ABSTRACTS / Bone 40 (2007) S22–S89
S27
or 10 mg/daily) improved BMD (+ 14.9 ± 9.8%), controlled bone fractures (no new fractures), and was safe and well tolerated. Ten years after, we investigated the BMD and long-term ALN safety in 30 of these patients (6 M, 24 F; age range 15– 28 years), affected by SLE (10), polyarticular juvenile idiopathic arthritis (JIA) (7), systemic JIA (6), dermatomyositis (5), other (2). Age at disease onset was 6.9 ± 4.2 years. During the follow-up, the disease was in remission in 18 patients, active in 7. Three patients were lost after 5–8 years; two died. Two young women got pregnant: one underwent voluntary abortion and the other is at the 8th month of a normal pregnancy. All patients were treated with glucocorticoids (GCs), and they are still taking GCs (duration 11.2 ± 6.1 years). In 6 patients, ALN was continued after Study 1. In 12, ALN was withdrawn at the end of Study 1, and restarted after 4.3 ± 2.9 years (daily or weekly). These 18 patients continued ALN for 8 months to 6 years after Study 1; 11 are still on treatment; 3 were shifted to risedronate. No side effects related to bisphosphonate use were observed in the long-term follow-up. 12 patients never took bisphosphonates after Study 1.In the 10-year follow-up, 3 fractures (Fx) occurred: 1 spine Fx after 15 months of ALN and 2 Fx after ALN withdrawal (limb after 8 months; spine after 4 years). At the last DXA evaluation, spine BMD Z-scores were: b -2 (- 3.4 ± 0.7) in 5 patients; between -2 and -1(- 1.5 ± 0.3) in 10; and N- 1 (0.16 ± 0.8) in 15. In the 18 ALN treated subjects, the BMD Z-score was − 1.5 ± 1.3, with a change of + 1.7 ± 0.9 versus that at the end of Study 1. In the 12 patients never treated with ALN after Study 1, Z-score was − 0.8 ± 1.4, with a change of +0.7 ± 0.8. In children/adolescents, alendronate seems to be safe also in long-term use. ALN use in childhood did not induce development or growth problems, nor interfered with the expected clinical course, according to the primary disease. Finally, a prolonged use of ALN seems to reduce the risk of new fractures, and to allow higher Z-score gains, notwithstanding the prolonged GCs therapy.
A 12-year-old boy was referred to our department after two subsequent fractures. At age 7 months, an unbalanced translocation t(9;14) (trisomy of the short arms of chromosome 9 and monosomy of chromosome 14) was discovered. His father and grandmother were phenotipically normal but had a balanced translocation t(9;14). He had a retarded growth (weight, height, psychomotor). Since age 4, he was on a milk-free diet for “suspected intolerance” to milk proteins. At age 11, he had an endocrinological evaluation: basal GH was normal, IgF1 reduced, arginine-stimulation showed a normal GH response. He had always been active (swimming, soccer, gymnastics). At age 12, after minor trauma, he suffered two fractures: first of left radial epiphysis, then of right wrist. He was sent to us for a deeper evaluation of phosphate and calcium metabolism and bone mineralization. Calcium, phosphate and magnesium were normal for age (9.1, 5 and 2.1 mg/dl respectively). Calciuria was reduced (56 mg/24 h); phosphaturia normal. Serum PTH moderately elevated (77.9 pg/ml). Vitamin D normal (25-OH 38 ng/ml; 1,25 (OH)2 D 61.5 pg/ml). Bone turnover markers were moderately increased with respect to the development stage (OC 45.8 ng/ml; urinary NTx 366 BCE/crea). IgF-1 levels were reduced. Thyroid function normal. Celiac disease antibodies negative. No other laboratory abnormalities were found. Bone age was 10 years, while the actual age was 12 years, 4 months. Bone density (spine, hip and total body with DXA) was significantly reduced. The Z-score was − 5.7 with respect to actual age, or − 4,2 with respect to bone age. The spine BMAD Z-score was − 3,9. This is the first report of reduced bone density in this genetic disease. It is obviously possible that in this boy, a calcium deficiency (due to unjustified dietary restrictions) has at least in part determined the reduced bone mass. The rarity of the disease makes specific studies impossible, but this case of reduced bone mass and recurrent fractures could justify bone mass evaluation and adequate therapeutic measures in cases of rare genetic disease, such as Trisomy 9p or translocation t(9;14).
doi:10.1016/j.bone.2007.04.011
doi:10.1016/j.bone.2007.04.012
Fragility fractures and low bone density described for the first time in unbalanced translocation t(9;14) M. Biggioggero 1, M.G. Dell’Orto 2, C. Fedeli 1, E. Viganò 2, C. Fossati 2, M.L. Bianchi 1 1 Bone Metabolism Unit, Istituto Auxologico Italiano IRCCS, Milano, Italy 2 Clin. Pediatrica, Università di Milano-Bicocca, Monza, Italy Trisomy 9p is a rare chromosomal abnormality caused by duplication of the short arm of chromosome 9, which determines many anomalies (central nervous system, craniofacial, heart, skeletal, skin). Translocation t(9;14) is an even rarer variant. Fragility fractures and low bone density have never been described in these conditions.
Use of total body MRI for the diagnosis of multifocal ON lesions: Case report N. Biltiau 1, B. Gillard 1, E. Bastianelli 2, V. Gangji 1 1 Rheumatology and physical and rehabilitation, Hôpital Erasme, Brussels, Belgium 2 Bone Therapeutics, Gosselies, Belgium Osteonecrosis (ON) is an affection characterized by an osteomedullar necrosis in the epiphyseal region of the joint. Glucocorticoid (GC) use and alcohol abuse are among the most recognized risk factors in Caucasians. ON can develop in one or be multifocal (N 3 joints). It usually evolves to subchondral fracture (stage 3) and collapse with the need for prosthetic replacement. However, the occurrence of ON over time is unknown.
S28
ABSTRACTS / Bone 40 (2007) S22–S89
A 30-year-old woman suffering from a cavernous angioma received high doses of GC for cerebral edema. Ten days after the GC treatment, she complained of pain in the knees and the ankles. The X-rays of were normal, but the magnetic resonance imaging (MRI) of the right knee showed an epiphyseal ON lesion of the external condylus involving 90% of its weight bearing portion without subchondral fracture. Three weeks after, a total body MRI (knees, hips, ankles, and shoulders, 4 mm, T1-weighted and T2-weighted images in the coronal plane) was realized showing large internal and external condylar and proximal tibial epiphyseal ON lesions in the left knee and a new internal condylar lesion in the right. In hips, there were epiphyseal hyposignal lesions on T2-weighted images and no lesion on T1-weighted images. The ankles images showed tibio-astragalar epiphyseal ON lesion without fracture. The shoulders were normal.
Eleven weeks after, 11, the total body MRI showed ON lesions of both hips involving 100% of the weight bearing portion and large epiphyseal ON lesions of the shoulders. Twenty-four weeks later, the X-rays of the affected joints were normal. Forty weeks later, the left hip evolved to the stage 3 (subchondral fracture). Forty-four weeks later, one shoulder showed a 1-mm subchondral fracture. The patient was treated with bone marrow implantation into the necrotic lesions of the knees, hips and shoulder. Conclusions: (i) In patients at risk, and complaining of joint pains, total body MRI should be proposed to search for ON. (ii) In ON confirmed patients, total body MRI should be performed every month during the first 3 months of the symptoms, as ON lesions develop over time. doi:10.1016/j.bone.2007.04.013
Genetic polymorphisms and fracture risk in children H.Z. Blades 1, W. Carlino 1, M. Durkie 2, A. Dalton 2, N.J. Bishop 1 1 Academic Child Health, University of Sheffield, Sheffield, United Kingdom 2 Molecular Genetics Service, Sheffield Children’s Hospital, Sheffield, United Kingdom Single nucleotide polymorphisms (SNPs) in genes important in bone metabolism may increase the risk of fracture, or affect bone mass and density. Whilst this has been the subject of extensive study in adults, there have been few such studies in children with data available only for effects of some SNPs on bone mass. We hypothesised that SNPs identified in adult cohorts, in particular, white premenopausal women, as being associated with increased fracture risk would demonstrate similar associations in children. We have recruited 93 cases (with fracture) and 32 controls (no current or previous fracture) from a target 200 per group by approaching families attending our A&E department with a history of trauma and suspected bony injury. The children underwent hip, spine and total body bone densitometry by DXA (Lunar Prodigy). DNA for SNP analysis was taken by buccal brushing. We tested for allelic distribution differences between the groups assessing COL1A1 Sp1, COL1A2 PvuII, TGFÎ21 c.29C N T, OPG g.163A N G and MTHFR c.677C N T SNPs. For COL1A1, there was a non-significant excess (11.7% vs. 7.1%) in children with fracture for the TT allele associated with increased fracture risk in adults. The COL1A1 TT allele was associated with lower bone mass in the lumbar spine (p = 0.043) after adjusting for body size. For COL1A2, there was a nonsignificant excess (8.0% vs. 4.1%) in children with fracture for the CC allele associated with increased fracture risk in adults. For TGFÎ21, there was a non-significant excess (46% vs. 27.6%) in children with fracture for the TT allele associated
S27
or 10 mg/daily) improved BMD (+ 14.9 ± 9.8%), controlled bone fractures (no new fractures), and was safe and well tolerated. Ten years after, we investigated the BMD and long-term ALN safety in 30 of these patients (6 M, 24 F; age range 15– 28 years), affected by SLE (10), polyarticular juvenile idiopathic arthritis (JIA) (7), systemic JIA (6), dermatomyositis (5), other (2). Age at disease onset was 6.9 ± 4.2 years. During the follow-up, the disease was in remission in 18 patients, active in 7. Three patients were lost after 5–8 years; two died. Two young women got pregnant: one underwent voluntary abortion and the other is at the 8th month of a normal pregnancy. All patients were treated with glucocorticoids (GCs), and they are still taking GCs (duration 11.2 ± 6.1 years). In 6 patients, ALN was continued after Study 1. In 12, ALN was withdrawn at the end of Study 1, and restarted after 4.3 ± 2.9 years (daily or weekly). These 18 patients continued ALN for 8 months to 6 years after Study 1; 11 are still on treatment; 3 were shifted to risedronate. No side effects related to bisphosphonate use were observed in the long-term follow-up. 12 patients never took bisphosphonates after Study 1.In the 10-year follow-up, 3 fractures (Fx) occurred: 1 spine Fx after 15 months of ALN and 2 Fx after ALN withdrawal (limb after 8 months; spine after 4 years). At the last DXA evaluation, spine BMD Z-scores were: b -2 (- 3.4 ± 0.7) in 5 patients; between -2 and -1(- 1.5 ± 0.3) in 10; and N- 1 (0.16 ± 0.8) in 15. In the 18 ALN treated subjects, the BMD Z-score was − 1.5 ± 1.3, with a change of + 1.7 ± 0.9 versus that at the end of Study 1. In the 12 patients never treated with ALN after Study 1, Z-score was − 0.8 ± 1.4, with a change of +0.7 ± 0.8. In children/adolescents, alendronate seems to be safe also in long-term use. ALN use in childhood did not induce development or growth problems, nor interfered with the expected clinical course, according to the primary disease. Finally, a prolonged use of ALN seems to reduce the risk of new fractures, and to allow higher Z-score gains, notwithstanding the prolonged GCs therapy.
A 12-year-old boy was referred to our department after two subsequent fractures. At age 7 months, an unbalanced translocation t(9;14) (trisomy of the short arms of chromosome 9 and monosomy of chromosome 14) was discovered. His father and grandmother were phenotipically normal but had a balanced translocation t(9;14). He had a retarded growth (weight, height, psychomotor). Since age 4, he was on a milk-free diet for “suspected intolerance” to milk proteins. At age 11, he had an endocrinological evaluation: basal GH was normal, IgF1 reduced, arginine-stimulation showed a normal GH response. He had always been active (swimming, soccer, gymnastics). At age 12, after minor trauma, he suffered two fractures: first of left radial epiphysis, then of right wrist. He was sent to us for a deeper evaluation of phosphate and calcium metabolism and bone mineralization. Calcium, phosphate and magnesium were normal for age (9.1, 5 and 2.1 mg/dl respectively). Calciuria was reduced (56 mg/24 h); phosphaturia normal. Serum PTH moderately elevated (77.9 pg/ml). Vitamin D normal (25-OH 38 ng/ml; 1,25 (OH)2 D 61.5 pg/ml). Bone turnover markers were moderately increased with respect to the development stage (OC 45.8 ng/ml; urinary NTx 366 BCE/crea). IgF-1 levels were reduced. Thyroid function normal. Celiac disease antibodies negative. No other laboratory abnormalities were found. Bone age was 10 years, while the actual age was 12 years, 4 months. Bone density (spine, hip and total body with DXA) was significantly reduced. The Z-score was − 5.7 with respect to actual age, or − 4,2 with respect to bone age. The spine BMAD Z-score was − 3,9. This is the first report of reduced bone density in this genetic disease. It is obviously possible that in this boy, a calcium deficiency (due to unjustified dietary restrictions) has at least in part determined the reduced bone mass. The rarity of the disease makes specific studies impossible, but this case of reduced bone mass and recurrent fractures could justify bone mass evaluation and adequate therapeutic measures in cases of rare genetic disease, such as Trisomy 9p or translocation t(9;14).
doi:10.1016/j.bone.2007.04.011
doi:10.1016/j.bone.2007.04.012
Fragility fractures and low bone density described for the first time in unbalanced translocation t(9;14) M. Biggioggero 1, M.G. Dell’Orto 2, C. Fedeli 1, E. Viganò 2, C. Fossati 2, M.L. Bianchi 1 1 Bone Metabolism Unit, Istituto Auxologico Italiano IRCCS, Milano, Italy 2 Clin. Pediatrica, Università di Milano-Bicocca, Monza, Italy Trisomy 9p is a rare chromosomal abnormality caused by duplication of the short arm of chromosome 9, which determines many anomalies (central nervous system, craniofacial, heart, skeletal, skin). Translocation t(9;14) is an even rarer variant. Fragility fractures and low bone density have never been described in these conditions.
Use of total body MRI for the diagnosis of multifocal ON lesions: Case report N. Biltiau 1, B. Gillard 1, E. Bastianelli 2, V. Gangji 1 1 Rheumatology and physical and rehabilitation, Hôpital Erasme, Brussels, Belgium 2 Bone Therapeutics, Gosselies, Belgium Osteonecrosis (ON) is an affection characterized by an osteomedullar necrosis in the epiphyseal region of the joint. Glucocorticoid (GC) use and alcohol abuse are among the most recognized risk factors in Caucasians. ON can develop in one or be multifocal (N 3 joints). It usually evolves to subchondral fracture (stage 3) and collapse with the need for prosthetic replacement. However, the occurrence of ON over time is unknown.
S28
ABSTRACTS / Bone 40 (2007) S22–S89
A 30-year-old woman suffering from a cavernous angioma received high doses of GC for cerebral edema. Ten days after the GC treatment, she complained of pain in the knees and the ankles. The X-rays of were normal, but the magnetic resonance imaging (MRI) of the right knee showed an epiphyseal ON lesion of the external condylus involving 90% of its weight bearing portion without subchondral fracture. Three weeks after, a total body MRI (knees, hips, ankles, and shoulders, 4 mm, T1-weighted and T2-weighted images in the coronal plane) was realized showing large internal and external condylar and proximal tibial epiphyseal ON lesions in the left knee and a new internal condylar lesion in the right. In hips, there were epiphyseal hyposignal lesions on T2-weighted images and no lesion on T1-weighted images. The ankles images showed tibio-astragalar epiphyseal ON lesion without fracture. The shoulders were normal.
Eleven weeks after, 11, the total body MRI showed ON lesions of both hips involving 100% of the weight bearing portion and large epiphyseal ON lesions of the shoulders. Twenty-four weeks later, the X-rays of the affected joints were normal. Forty weeks later, the left hip evolved to the stage 3 (subchondral fracture). Forty-four weeks later, one shoulder showed a 1-mm subchondral fracture. The patient was treated with bone marrow implantation into the necrotic lesions of the knees, hips and shoulder. Conclusions: (i) In patients at risk, and complaining of joint pains, total body MRI should be proposed to search for ON. (ii) In ON confirmed patients, total body MRI should be performed every month during the first 3 months of the symptoms, as ON lesions develop over time. doi:10.1016/j.bone.2007.04.013
Genetic polymorphisms and fracture risk in children H.Z. Blades 1, W. Carlino 1, M. Durkie 2, A. Dalton 2, N.J. Bishop 1 1 Academic Child Health, University of Sheffield, Sheffield, United Kingdom 2 Molecular Genetics Service, Sheffield Children’s Hospital, Sheffield, United Kingdom Single nucleotide polymorphisms (SNPs) in genes important in bone metabolism may increase the risk of fracture, or affect bone mass and density. Whilst this has been the subject of extensive study in adults, there have been few such studies in children with data available only for effects of some SNPs on bone mass. We hypothesised that SNPs identified in adult cohorts, in particular, white premenopausal women, as being associated with increased fracture risk would demonstrate similar associations in children. We have recruited 93 cases (with fracture) and 32 controls (no current or previous fracture) from a target 200 per group by approaching families attending our A&E department with a history of trauma and suspected bony injury. The children underwent hip, spine and total body bone densitometry by DXA (Lunar Prodigy). DNA for SNP analysis was taken by buccal brushing. We tested for allelic distribution differences between the groups assessing COL1A1 Sp1, COL1A2 PvuII, TGFÎ21 c.29C N T, OPG g.163A N G and MTHFR c.677C N T SNPs. For COL1A1, there was a non-significant excess (11.7% vs. 7.1%) in children with fracture for the TT allele associated with increased fracture risk in adults. The COL1A1 TT allele was associated with lower bone mass in the lumbar spine (p = 0.043) after adjusting for body size. For COL1A2, there was a nonsignificant excess (8.0% vs. 4.1%) in children with fracture for the CC allele associated with increased fracture risk in adults. For TGFÎ21, there was a non-significant excess (46% vs. 27.6%) in children with fracture for the TT allele associated