L R Ranganath1,2, M Khedr3, S Vinjamuri4, J A Gallagher5. 1. Departments of Clinical Biochemistry and Metabolic Medicine, Royal Liverpool University Hospital, Prescot Street, Liverpool, L7 8XP, UK. lrang@liv.ac.uk. 2. IACD, University of Liverpool, William Henry Duncan Building, West Derby Street, Liverpool, L7 8TX, UK. lrang@liv.ac.uk. 3. Departments of Clinical Biochemistry and Metabolic Medicine, Royal Liverpool University Hospital, Prescot Street, Liverpool, L7 8XP, UK. 4. Nuclear Medicine, Royal Liverpool University Hospital, Prescot Street, Liverpool, L7 8XP, UK. 5. IACD, University of Liverpool, William Henry Duncan Building, West Derby Street, Liverpool, L7 8TX, UK.
Abstract
Osteoporosis and fractures are common features of alkaptonuria. INTRODUCTION: A large cohort of alkaptonuria (AKU) patients was studied to better recognise and characterise osteoporosis and fractures in AKU. METHODS: Assessments including questionnaire analysis, DEXA and CT densitometry at the neck of femur (FN), total hip (TH) and lumbar spine (LS) were performed on patients at baseline when 2 mg nitisinone was commenced, and yearly thereafter. Blood and urine samples were collected for chemical measurement. CT BMD Z-scores were generated. RESULTS: Between June 2007 and March 2020, 87 AKU patients attended the NAC. At baseline, there were 48 fractures in 39 patients. Prevalence of osteoporosis was 3.1 at FN, 10.8 at TH and 24.7% at LS respectively. Prevalence of fragility fractures was greatly increased at 44.8%. The group with fractures showed increased ochronosis scores (p < 0.05). CT LS showed an inverse relationship with fractures (R = - 0.28; p < 0.05). CT LS was significantly lower in the fracture group (p < 0.002). Following nitisinone only, CT FN and CT TH decreased significantly (p < 0.05 and 0.01 respectively). Following nitisinone plus antiresorptive therapy, CT FN, CT TH and CT LS all increased significantly (p < 0.05, 0.05 and 0.001 respectively). However, patients on nitisinone plus antiresorptive had more fractures than nitisinone and no-treatment groups (p < 0.05). CONCLUSIONS: Osteopenia and fragility fractures are common in AKU.. Anti-resorptive therapy increased BMD in AKU without decreasing fragility fractures. Bone densitometry measurements by DXA are less reliable than quantitative CT at the LS in AKU.
Osteoporosis and fractures are common features of alkaptonuria. INTRODUCTION: A large cohort of alkaptonuria (AKU) patients was studied to better recognise and characterise osteoporosis and fractures in AKU. METHODS: Assessments including questionnaire analysis, DEXA and CT densitometry at the neck of femur (FN), total hip (TH) and lumbar spine (LS) were performed on patients at baseline when 2 mg nitisinone was commenced, and yearly thereafter. Blood and urine samples were collected for chemical measurement. CT BMD Z-scores were generated. RESULTS: Between June 2007 and March 2020, 87 AKUpatients attended the NAC. At baseline, there were 48 fractures in 39 patients. Prevalence of osteoporosis was 3.1 at FN, 10.8 at TH and 24.7% at LS respectively. Prevalence of fragility fractures was greatly increased at 44.8%. The group with fractures showed increased ochronosis scores (p < 0.05). CT LS showed an inverse relationship with fractures (R = - 0.28; p < 0.05). CT LS was significantly lower in the fracture group (p < 0.002). Following nitisinone only, CT FN and CT TH decreased significantly (p < 0.05 and 0.01 respectively). Following nitisinone plus antiresorptive therapy, CT FN, CT TH and CT LS all increased significantly (p < 0.05, 0.05 and 0.001 respectively). However, patients on nitisinone plus antiresorptive had more fractures than nitisinone and no-treatment groups (p < 0.05). CONCLUSIONS:Osteopenia and fragility fractures are common in AKU.. Anti-resorptive therapy increased BMD in AKU without decreasing fragility fractures. Bone densitometry measurements by DXA are less reliable than quantitative CT at the LS in AKU.
Authors: David B Ascher; Ottavia Spiga; Martina Sekelska; Douglas E V Pires; Andrea Bernini; Monica Tiezzi; Jana Kralovicova; Ivana Borovska; Andrea Soltysova; Birgitta Olsson; Silvia Galderisi; Vittoria Cicaloni; Lakshminarayan Ranganath; Annalisa Santucci; Andrea Zatkova Journal: Eur J Hum Genet Date: 2019-02-08 Impact factor: 4.246
Authors: Mohammad S Z Ahmad; Mahmoud Ahmed; Milad Khedr; Alfredo Borgia; Andrea Madden; Lakshminarayan R Ranganath; Stephen Kaye Journal: JIMD Rep Date: 2022-04-09
Authors: Lakshminarayan R Ranganath; Anna M Milan; Andrew T Hughes; Milad Khedr; Brendan P Norman; Mohammed Alsbou; Richard Imrich; Matthew Gornall; Nicolas Sireau; James A Gallagher; Richard Jackson Journal: JIMD Rep Date: 2021-11-11