Background: a high prevalence of vertebral fractures, despite normal bone mineral density (BMD), is reported in acromegalic patients in both the active and inactive phases of the disease. Aim of the study: to analyze the prevalence of vertebral fractures, bone turnover, BMD and histomorphometric parameters including bone microarchitecture in a group of acromegalic patients. Patients and methods: 42 acromegalic patients (26 males, 16 females, mean age 58 ±12,5 and 58,8 ±13,8 years), divided in 2 subgroups: one with active disease and one in remission (13, 29 patients respectively) underwent bone turnover evaluation (serum calcium, serum phosphate, PTH, 25- hydroxyvitamin (OH) D , ALP, CTX, urinary calcium/creatinine) and bone densitometry by Dual-Energy X-Ray Absorptiometry (DXA). Vertebral fractures were assessed by morphometric analysis during DXA. In 4 patients iliac crest bone biopsy was performed.Results: the prevalence of vertebral fractures was 64% in the whole population, 69% in the active group, 59% in the remission group. Among fractured patients, vertebral t-score was normal in 59% and it showed osteoporosis in only 11%. Vertebral BMD was higher in fractured patients compared to non-fractured (mean SD 1,108 ±0,175 vs 0,961± 0,118 g/cm2, p=0,009), also considering the active (1,147±0,241 vs 1,107±0,169 g/cm2) and inactive subgroups (1,093 ±0,15 vs 0,945 ±0,106g/cm2, p0,01). Disease duration was significantly higher in fractured compared to non-fractured patients (respectively 8,67 ±6,65 and 6,93 ±3,41 years, p<0,05). As regards bone metabolism parameters, urinary calcium/creatinine was significantly higher in fractured patients compared to non-fractured patients (0,125 ±0,096 vs 0,074 ±0,031, p<0,01). 25-OH vitamin D was low in both groups (fractures 24,93 ±11,5 ng/ml, non-fractured patients 25,02 ±7,28 ng/ml). Hypogonadism was a risk factor for vertebral fractures in active patients (p=0,04). The preliminary results regarding histomorphometric evaluation showed a greater cortical thickness and an increased porosity compared to that of normal subjects (cortical width 1882±250 vs 816±291 μm, cortical porosity index 10 ±4% vs 5,79 ±2,76%). IGF-1 positively correlated with porosity index (p<0,05).Conclusions: our data confirm a high prevalence of vertebral fractures in acromegalic patients despite a normal BMD. This apparent paradox could be explained by an increased cortical thickness associated with abnormal cortical porosity, mediated by IGF-1.
Bone Fragility in Acromegalic Patients: A Mystery Almost Solved?
MICHELETTI, Valentina;DAVI', Maria Vittoria;VALENTI, Maria Teresa;DALLE CARBONARE, Luca Giuseppe;FRANCIA, Giuseppe
2013-01-01
Abstract
Background: a high prevalence of vertebral fractures, despite normal bone mineral density (BMD), is reported in acromegalic patients in both the active and inactive phases of the disease. Aim of the study: to analyze the prevalence of vertebral fractures, bone turnover, BMD and histomorphometric parameters including bone microarchitecture in a group of acromegalic patients. Patients and methods: 42 acromegalic patients (26 males, 16 females, mean age 58 ±12,5 and 58,8 ±13,8 years), divided in 2 subgroups: one with active disease and one in remission (13, 29 patients respectively) underwent bone turnover evaluation (serum calcium, serum phosphate, PTH, 25- hydroxyvitamin (OH) D , ALP, CTX, urinary calcium/creatinine) and bone densitometry by Dual-Energy X-Ray Absorptiometry (DXA). Vertebral fractures were assessed by morphometric analysis during DXA. In 4 patients iliac crest bone biopsy was performed.Results: the prevalence of vertebral fractures was 64% in the whole population, 69% in the active group, 59% in the remission group. Among fractured patients, vertebral t-score was normal in 59% and it showed osteoporosis in only 11%. Vertebral BMD was higher in fractured patients compared to non-fractured (mean SD 1,108 ±0,175 vs 0,961± 0,118 g/cm2, p=0,009), also considering the active (1,147±0,241 vs 1,107±0,169 g/cm2) and inactive subgroups (1,093 ±0,15 vs 0,945 ±0,106g/cm2, p0,01). Disease duration was significantly higher in fractured compared to non-fractured patients (respectively 8,67 ±6,65 and 6,93 ±3,41 years, p<0,05). As regards bone metabolism parameters, urinary calcium/creatinine was significantly higher in fractured patients compared to non-fractured patients (0,125 ±0,096 vs 0,074 ±0,031, p<0,01). 25-OH vitamin D was low in both groups (fractures 24,93 ±11,5 ng/ml, non-fractured patients 25,02 ±7,28 ng/ml). Hypogonadism was a risk factor for vertebral fractures in active patients (p=0,04). The preliminary results regarding histomorphometric evaluation showed a greater cortical thickness and an increased porosity compared to that of normal subjects (cortical width 1882±250 vs 816±291 μm, cortical porosity index 10 ±4% vs 5,79 ±2,76%). IGF-1 positively correlated with porosity index (p<0,05).Conclusions: our data confirm a high prevalence of vertebral fractures in acromegalic patients despite a normal BMD. This apparent paradox could be explained by an increased cortical thickness associated with abnormal cortical porosity, mediated by IGF-1.
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