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Letter to the Editor
Adefovir-induced osteomalacia and hypophosphatemia
Osteomalacia e hipofosfatemia inducida por adefovir
José Antonio López Medina, Víctor José Simón Frapolli
Corresponding author
victorsimonfrapo.med@gmail.com

Corresponding author.
, Francisco José Tinahones Madueño
Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria, Málaga, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Osteomalacia is a bone metabolism disorder characterized by a deficient mineralization of the organic bone matrix&#46; During childhood&#44; this disorder is known by the name of rickets and also causes cartilage growth alterations&#46; Calcium and phosphate salts are necessary for the proper formation of the bone architecture&#46; Because calcium absorption is very closely linked to vitamin D&#44; an alteration in the function of either of these factors results in an accumulation of unmineralized osteoid matrix and a decrease in bone strength&#46; Osteomalacia has multiple known causes&#44; including vitamin D alterations&#44; phosphorus metabolism alterations&#44; certain drugs&#44; oncological diseases&#44; and genetic causes&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Adefovir is an antiretroviral drug indicated for the treatment of chronic hepatitis B in adults with a compensated liver disease with evidence of viral replication&#46; One of its adverse effects is renal tubule involvement&#44; which results in hypophosphatemia&#44; hypouricemia&#44; proteinuria&#44; and glycosuria&#46; Hypophosphatemia can cause osteomalacia by inhibiting bone mineralization&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In his paper we describe the clinical case of a 53-year-old man who was referred to our Endocrinology Department for a phosphorus-calcium metabolism study due to presenting with multiple pathological bone fractures within the last year&#44; pain in his lower limbs&#44; and hypophosphatemia&#46; His personal medical history included arterial hypertension under treatment with candesartan 16&#8239;mg&#47;day&#44; as well as chronic hepatitis B under treatment with adefovir 10&#8239;mg&#47;day for 5 years&#46; Physical examination revealed a weight of 75&#8239;kg&#44; a height of 170&#8239;cm&#44; and a body mass index &#40;BMI&#41; of 25&#46;9&#8239;kg&#47;m<span class="elsevierStyleSup">2</span>&#46; He had normal vital signs and no neurological focalities&#44; but he complained of pain on palpation of the dorsal spine and multiple ribs of the right costal curvature&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Blood tests revealed the following&#58; normal complete blood count and erythrocyte sedimentation rate&#44; creatinine levels of 1&#46;13&#8239;mg&#47;dl&#44; estimated glomerular filtration rate of 64&#8239;ml&#47;min&#44; serum calcium levels of 9&#8239;mg&#47;dl &#40;normal range&#58; 8&#46;5&#8211;10&#46;5&#41;&#44; phosphorus levels of 1&#46;8&#8239;mg&#47;dl &#40;normal range&#58; 2&#46;2&#8211;4&#46;7&#41;&#44; vitamin D levels of 16&#8239;ng&#47;mL &#40;normal range&#58; 20&#8211;50&#41;&#44; alkaline phosphatase levels of 218 U&#47;L &#40;normal range&#58; 45&#8211;129&#41;&#44; intact parathyroid hormone levels &#40;PTHi&#41; of 38&#8239;pg&#47;mL &#40;normal range&#58; 10&#8211;65&#41;&#44; normal transaminase levels&#44; uric acid levels of 2&#46;5&#8239;mg&#47;dl &#40;normal range&#58; 3&#46;4&#8211;7&#41;&#44; and a tubular phosphate reabsorption rate of 47&#37; &#40;normal &#62;80&#37;&#41;&#46; A urine analysis yielded the below figures&#58; microalbuminuria 152&#8239;mg&#47;day &#40;normal figure&#58; &#60;30&#8239;mg&#47;day&#41; and glycosuria &#40;&#62;100&#8239;mg&#47;day&#41;&#46; In addition&#44; he had a normal protein panel and thyroid stimulating hormone &#40;TSH&#41; levels of 1&#46;36 IU&#47;mL &#40;normal range&#58; 0&#46;35&#8211;5&#46;50&#41;&#44; negativity for antinuclear antibodies and the HLA-B27 antigen&#44; and a C-terminal fibroblast growth factor 23 &#40;cFGF-23&#41; concentration of 72&#8239;kRU&#47;L &#40;normal range&#58; 26&#8211;110&#41;&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">A chest X-ray showed non-displaced fractures in the posterior&#44; proximal segments of the sixth and eighth ribs of the right costal curvature&#46; A bone scan showed multiple foci of radiopharmaceutical uptake in the rib cages&#44; the sacroiliac joint&#44; and chondromalacia patellae&#46; In addition&#44; a compression fracture in the upper endplates of vertebral bodies T5&#8211;T6 and T7&#44; as well as traces of rib fractures in the areas described earlier&#44; were identified in a magnetic resonance imaging &#40;MRI&#41; scan of the dorsal spine&#46; A scintigram with octreotide-IN 111 revealed no alterations&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">In view of these findings&#44; and given the suspected diagnosis of adefovir-induced hypophosphatemic osteomalacia&#44; we decided to discontinue this drug&#44; observing a progressive improvement of the patient&#8217;s symptoms and laboratory parameters thereafter&#46; A follow-up examination performed three months later revealed serum phosphorus levels of 2&#46;7&#8239;mg&#47;dl &#40;without oral supplementation&#41; and normalization of the phosphate tubular reabsorption parameters&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Adefovir is a drug indicated for the treatment of chronic hepatitis B&#44; as it inhibits reverse transcriptase and DNA synthetase&#44; thereby preventing the proliferation of the hepatitis B virus&#46; It is a well-known fact that this drug can cause nephrotoxicity when used at high doses and for prolonged periods of time due to causing damage to the proximal renal tubule&#44; which results in deficient tubular phosphate reabsorption and hypophosphatemic osteomalacia&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> However&#44; these effects have also been described in patients taking a lower dose of adefovir of 10&#8239;mg&#47;day&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Osteomalacia is a difficult clinical entity to diagnose&#44; as its symptoms are often non-specific&#46; It usually manifests with pain&#44; proximal muscle weakness&#44; and&#44; at advanced stages&#44; bone fractures&#44; which are very common in the ribs&#46; The most prevalent cause of osteomalacia is a vitamin D deficiency&#44; which usually presents with normal calcium and phosphorus levels&#44; a low renal calcium excretion&#44; a high renal phosphate excretion&#44; increased PTH levels&#44; and low vitamin D levels&#46; However&#44; hypophosphatemic osteomalacia caused by certain drugs presents with low phosphorus levels&#44; elevated alkaline phosphatase&#44; and normal calcium&#44; PTH&#44; and vitamin D levels&#46; The most characteristic radiological alterations found in cases of osteomalacia are pseudofractures or the presence of Looser-Milkman lines&#44; which are more frequently detected in the ribs&#44; hips&#44; scapulae&#44; and lower limbs&#44; can be seen in a plain X-ray&#44; and can evolve into complete fractures&#46; Bone scans are very useful and sensitive in locating these alterations&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Ethical responsibilities</span><p id="par0045" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Protection of people and animals&#46;</span> The authors of this paper declare that no experiments were carried out on humans or animals for the conduct of this research&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Data confidentiality&#46;</span> The authors of this paper declare that they followed their site&#8217;s protocols regarding the publication of patient data and that all patients included in the study received sufficient information and provided their written informed consent to participate in the study&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Right to privacy and informed consent&#46;</span> The authors declare that no patient data appear in this article&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflicts of interest</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest&#46;</p></span></span>"
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ISSN: 23870206
Original language: English
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