Letter to the Editor
Ochronosis and Osteoporosis: A Case Report
Ocronosis y osteoporosis: a propósito de un caso
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María Dolores Sánchez González" "autores" => array:4 [ 0 => array:4 [ "nombre" => "Ismael" "apellidos" => "Calero Paniagua" "email" => array:2 [ 0 => "ismaelcaleropaniagua@yahoo.es" 1 => "feel_the_croquet@yahoo.es" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Carlos Alberto" "apellidos" => "Montilla Morales" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Tatiana Elizabeth" "apellidos" => "Carranco Medina" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "María Dolores" "apellidos" => "Sánchez González" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Reumatología, Hospital Universitario de Salamanca, Salamanca, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Ocronosis y osteoporosis: a propósito de un caso" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1172 "Ancho" => 1301 "Tamanyo" => 126604 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Calcification of intervertebral discs, fusion of vertebrae, diffuse vertebral sclerosis, bony bridge in pubic symphysis; (B) calcification of intervertebral discs, fusion of vertebral bodies with diffuse sclerosis, vertebral fracture of the third lumbar vertebra (arrow).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Alkaptonuria is a hereditary metabolic disorder caused by homogentisate 1,2-dioxygenase (HGD) deficiency. Oxidative conversion of HGD leads to the production of a melanin polymer, whose accumulation in the connective tissue causes a characteristic pigmentation known as ochronosis. The fusion of the ochronotic pigment to the conjunctive tissue causes a multisystem disorder characterized by premature spondyloarthritis. Other systemic characteristics include calculi (salivary, renal, biliary), renal failure, respiratory failure, hearing loss, aortic valve disease, osteoporosis and rupture of tendons, muscles and ligaments.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">1–4</span></a> Prolapsed discs are rare<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">5</span></a> and vertebral fracture is an exceptional complication, with only one case reported in the literature.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">6</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We present the case of a 55-year-old male patient who had been referred to our consultation to evaluate chronic thoracolumbar pain. Findings of the physical examination included an important reduction in spinal column mobility and grey-brown pigmentation of both sclerae. After the radiology study (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), we decided to measure HGD levels in urine (4218.0<span class="elsevierStyleHsp" style=""></span>mg/L; normal<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>mg/L), which confirmed the suspected diagnosis of ochronosis. The patient began with physical therapy sessions, and the improvement was noticeable. At that time (January 2004), dual-energy X-ray absorptiometry was used to determine the bone mineral density (BMD) of the lumbar spine (LS), which showed a <span class="elsevierStyleItalic">T</span>-score of −3.0 SD. The patient initiated treatment with risedronate (75<span class="elsevierStyleHsp" style=""></span>mg weekly). In March 2005, BMD was evaluated once again, with a <span class="elsevierStyleItalic">T</span>-score of −2.4 SD in the LS, −30 SD in the femoral neck (FN) and −2.7 SD in the total hip (TH). Treatment was continued with bisphosphonates, and then changed to alendronate (70<span class="elsevierStyleHsp" style=""></span>mg weekly). In June 2007, BMD showed improved <span class="elsevierStyleItalic">T</span>-scores in the LS (−1.7 SD) and TH (−2.3 SD) and stabilization in the FN (−3.0 SD). In January 2013, the patient came to our emergency department with acute back pain, but reported having had no trauma. Lateral LS radiography revealed a fracture of the third lumbar vertebra (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). After that incident, we opted to begin treatment with subcutaneous teriparatide. To date (November 2014), no new vertebral fractures have appeared.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">There are several hypotheses that attempt to explain how the accumulation of HGD leads to ochronosis and arthropathy. These include the interference of HGD with the intertwining of collagen fibres and inflammatory response triggered by free radicals formed by the oxidation of HGD.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">2</span></a> As for the development of osteoporosis, Aliberti et al. indicated that ochronosis can be associated with a higher rate of bone resorption, which would involve accelerated bone mass loss.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">7</span></a> The same authors showed the ineffectiveness of alendronate for reverting the process of bone mass loss in a considerable number of patients with ochronosis and osteoporosis. This suggests that the existence of a specific physiopathological mechanism (microlesions of the matrix, viability of the osteocytes and deterioration of the collagen network), not involved in the pharmacodynamics of bisphosphonates, could be responsable.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">8</span></a> Although our patient had advanced-stage disease (stage <span class="elsevierStyleSmallCaps">IV</span>, osseous ankylosis<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">9</span></a>) and in spite of the reported general tendency, his BMD progressively increased thanks to treatment with bisphosphonates. It did not, however, prevent the appearance of a vertebral fracture due to fragility. Given that treatment with bisphosphonates is well tolerated and can improve BMD in some cases, this treatment could be useful in patients with ochronosis and osteoporosis. Its indication should be individualized until new scientific evidence is reported.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Calero Paniagua I, Montilla Morales CA, Carranco Medina TE, Sánchez González MD. Ocronosis y osteoporosis: a propósito de un caso. Reumatol Clin. 2015;11:330–331.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1172 "Ancho" => 1301 "Tamanyo" => 126604 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Calcification of intervertebral discs, fusion of vertebrae, diffuse vertebral sclerosis, bony bridge in pubic symphysis; (B) calcification of intervertebral discs, fusion of vertebral bodies with diffuse sclerosis, vertebral fracture of the third lumbar vertebra (arrow).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:9 [ 0 => array:3 [ "identificador" => "bib0050" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Recent advances in managemet of alkaptonuria (invited review; best practice article)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "L.R. 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Proietta" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10067-006-0390-3" "Revista" => array:6 [ "tituloSerie" => "Clin Rheumatol" "fecha" => "2007" "volumen" => "26" "paginaInicial" => "729" "paginaFinal" => "735" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16924393" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0090" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A simplified staging system based on the radiological findings in different stages of ochronotic spondyloarthropathy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "I. Jebaraj" 1 => "B.R. Chacko" 2 => "G.K. Chiramel" 3 => "T. Matthai" 4 => "A. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 5 | 4 | 9 |
| 2024 October | 34 | 29 | 63 |
| 2024 September | 34 | 14 | 48 |
| 2024 August | 63 | 39 | 102 |
| 2024 July | 46 | 34 | 80 |
| 2024 June | 47 | 30 | 77 |
| 2024 May | 62 | 40 | 102 |
| 2024 April | 55 | 39 | 94 |
| 2024 March | 56 | 36 | 92 |
| 2024 February | 58 | 25 | 83 |
| 2024 January | 31 | 18 | 49 |
| 2023 December | 34 | 35 | 69 |
| 2023 November | 56 | 42 | 98 |
| 2023 October | 36 | 36 | 72 |
| 2023 September | 73 | 48 | 121 |
| 2023 August | 52 | 15 | 67 |
| 2023 July | 61 | 31 | 92 |
| 2023 June | 75 | 22 | 97 |
| 2023 May | 56 | 23 | 79 |
| 2023 April | 48 | 8 | 56 |
| 2023 March | 60 | 40 | 100 |
| 2023 February | 63 | 31 | 94 |
| 2023 January | 51 | 33 | 84 |
| 2022 December | 48 | 35 | 83 |
| 2022 November | 56 | 27 | 83 |
| 2022 October | 60 | 31 | 91 |
| 2022 September | 42 | 34 | 76 |
| 2022 August | 45 | 53 | 98 |
| 2022 July | 38 | 36 | 74 |
| 2022 June | 37 | 45 | 82 |
| 2022 May | 54 | 42 | 96 |
| 2022 April | 55 | 48 | 103 |
| 2022 March | 61 | 36 | 97 |
| 2022 February | 57 | 29 | 86 |
| 2022 January | 57 | 37 | 94 |
| 2021 December | 57 | 45 | 102 |
| 2021 November | 59 | 55 | 114 |
| 2021 October | 89 | 78 | 167 |
| 2021 September | 48 | 41 | 89 |
| 2021 August | 35 | 64 | 99 |
| 2021 July | 45 | 53 | 98 |
| 2021 June | 52 | 67 | 119 |
| 2021 May | 62 | 66 | 128 |
| 2021 April | 218 | 112 | 330 |
| 2021 March | 105 | 59 | 164 |
| 2021 February | 50 | 34 | 84 |
| 2021 January | 63 | 18 | 81 |
| 2020 December | 60 | 34 | 94 |
| 2020 November | 76 | 50 | 126 |
| 2020 October | 67 | 25 | 92 |
| 2020 September | 59 | 41 | 100 |
| 2020 August | 122 | 41 | 163 |
| 2020 July | 93 | 31 | 124 |
| 2020 June | 111 | 41 | 152 |
| 2020 May | 42 | 15 | 57 |
| 2020 April | 58 | 30 | 88 |
| 2020 March | 11 | 2 | 13 |
| 2020 February | 1 | 0 | 1 |
| 2019 August | 2 | 0 | 2 |
| 2018 December | 2 | 0 | 2 |
| 2018 May | 5 | 0 | 5 |
| 2018 April | 50 | 8 | 58 |
| 2018 March | 91 | 6 | 97 |
| 2018 February | 40 | 2 | 42 |
| 2018 January | 28 | 4 | 32 |
| 2017 December | 33 | 8 | 41 |
| 2017 November | 24 | 6 | 30 |
| 2017 October | 30 | 7 | 37 |
| 2017 September | 28 | 7 | 35 |
| 2017 August | 27 | 6 | 33 |
| 2017 July | 44 | 16 | 60 |
| 2017 June | 36 | 7 | 43 |
| 2017 May | 61 | 4 | 65 |
| 2017 April | 39 | 7 | 46 |
| 2017 March | 28 | 14 | 42 |
| 2017 February | 41 | 4 | 45 |
| 2017 January | 33 | 10 | 43 |
| 2016 December | 60 | 15 | 75 |
| 2016 November | 62 | 15 | 77 |
| 2016 October | 92 | 9 | 101 |
| 2016 September | 85 | 6 | 91 |
| 2016 August | 65 | 7 | 72 |
| 2016 July | 34 | 6 | 40 |
| 2015 December | 5 | 38 | 43 |
| 2015 November | 1 | 56 | 57 |
| 2015 October | 6 | 50 | 56 |
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