ABSTRACT
INTRODUCTION: l´ostéomalacie est une ostéopathie raréfiante secondaire à un défaut de minéralisation de la trame osseuse. Son diagnostic est le plus souvent porté au stade de complications car ses manifestations sont diverses et souvent méconnues. But: étudier les profils cliniques, biologiques et étiologiques de l´ostéomalacie. MÉTHODES: il s´agit d´une étude rétrospective colligeant tous les dossiers d´ostéomalacie hospitalisés entre Mai 2006 et Janvier 2014. RÉSULTATS: notre étude a inclus 30 cas d´ostéomalacie avec un âge moyen de 55 ans [29 ans - 82 ans]. Une nette prédominance féminine était notée avec un sexe ratio de 0.11. Tous nos patients avaient un régime hypo-calcique et une seule patiente avait un régime suffisant en vitamine D. Tous les patients présentaient des douleurs osseuses à l´examen et 80% d´entre eux présentaient un trouble de la marche. Les déformations ont été notées dans la moitié des cas. Sur le plan biologique, la baisse de la 25 OH vit D était constamment retrouvée suivie par l´augmentation des phosphatases alcalines (90%), alors que l´hypocalcémie et l´hypophosphorémie étaient présentes chez respectivement 46,6 et 50% des cas. La carence en vitamine D était la cause retenue dans la majorité des cas (86.6%). Une malabsorption a été notée dans 2 cas. CONCLUSION: à travers notre travail, nous avons mis en évidence plusieurs formes évoluées d´OM. Ceci impose un dépistage précoce et une enquête étiologique minutieuse.
Subject(s)
Calcium/blood , Osteomalacia/diagnosis , Pain/etiology , Vitamin D Deficiency/complications , Adult , Aged , Aged, 80 and over , Calcium, Dietary/administration & dosage , Female , Humans , Hypophosphatemia/epidemiology , Male , Middle Aged , Osteomalacia/etiology , Osteomalacia/physiopathology , Retrospective Studies , Vitamin D Deficiency/epidemiologyABSTRACT
Fibroblast growth factor 23 (FGF23), one of the endocrine fibroblast growth factors, is a principal regulator in the maintenance of serum phosphorus concentration. Binding to its cofactor αKlotho and a fibroblast growth factor receptor is essential for its activity. Its regulation and interaction with other factors in the bone-parathyroid-kidney axis is complex. FGF23 reduces serum phosphorus concentration through decreased reabsorption of phosphorus in the kidney and by decreasing 1,25 dihydroxyvitamin D (1,25(OH)2D) concentrations. Various FGF23-mediated disorders of renal phosphate wasting share similar clinical and biochemical features. The most common of these is X-linked hypophosphatemia (XLH). Additional disorders of FGF23 excess include autosomal dominant hypophosphatemic rickets, autosomal recessive hypophosphatemic rickets, fibrous dysplasia, and tumor-induced osteomalacia. Treatment is challenging, requiring careful monitoring and titration of dosages to optimize effectiveness and to balance side effects. Conventional therapy for XLH and other disorders of FGF23-mediated hypophosphatemia involves multiple daily doses of oral phosphate salts and active vitamin D analogs, such as calcitriol or alfacalcidol. Additional treatments may be used to help address side effects of conventional therapy such as thiazides to address hypercalciuria or nephrocalcinosis, and calcimimetics to manage hyperparathyroidism. The recent development and approval of an anti-FGF23 antibody, burosumab, for use in XLH provides a novel treatment option.
Subject(s)
Fibroblast Growth Factors , Hypophosphatemia/therapy , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Familial Hypophosphatemic Rickets/physiopathology , Familial Hypophosphatemic Rickets/therapy , Fibroblast Growth Factor-23 , Fibroblast Growth Factors/genetics , Fibroblast Growth Factors/metabolism , Humans , Hypophosphatemia/physiopathology , Osteomalacia/physiopathology , Osteomalacia/therapy , Phosphates/metabolism , Phosphates/therapeutic useABSTRACT
OBJECTIVE: To investigate the predictors of hypophosphatemic osteomalacia induced by adefovir dipivoxil (ADV) and to monitor for early detection. PATIENTS AND METHODS: Hospitalized patients who were diagnosed with ADV-related hypo-phosphatemic osteomalacia were recruited and retrospectively analyzed in our hospital from January 2012 to December 2016. A telephone interview was conducted at 1, 3, 6, 9, 12, and 24 months after cessation of ADV. RESULTS: In the 8 patients enrolled in the study, the hypophosphatemic osteomalacia symptoms developed at an average of 5.14 (4-7) years since ADV treatment (10 mg/d). The average alkaline phosphatase (ALP) level was 279.50 (137-548) U/L, which was significantly higher than the normal level (45-125 U/L). The serum phosphorus level was an average of 0.59 (0.43-0.69) mmol/L, which was lower than the normal range (2.06-2.60 mmol/L). Serum calcium levels of the enrolled patients remained within normal limits. Reduced estimated glomerular filtration rate (eGFR <29 mL/min/1.73 m2) was seen in 4 cases. The clinical manifestations were mainly progressive systemic bone and joint pain, frequent fractures, trouble in walking, height reduction (4-6 cm), and so on. After cessation of ADV, symptoms like bone pain resolved gradually. Serum phosphorus level restored to normal in 4.5 months after the withdrawal of ADV. However, in 4 patients, renal function failed to return to normal in 24 months. CONCLUSION: More attention should be paid to the duration of ADV treatment. The level of serum phosphorus and ALP, as well as renal function, should be monitored for early detection of potential adverse drug reactions.
Subject(s)
Adenine/analogs & derivatives , Hypophosphatemia/chemically induced , Organophosphonates/administration & dosage , Organophosphonates/adverse effects , Osteomalacia/chemically induced , Reverse Transcriptase Inhibitors/administration & dosage , Adenine/administration & dosage , Adenine/adverse effects , Adult , Aged , Alkaline Phosphatase/blood , Biomarkers/blood , China , Cross-Sectional Studies , Drug Monitoring , Early Diagnosis , Female , Glomerular Filtration Rate/drug effects , Humans , Hypophosphatemia/blood , Hypophosphatemia/diagnosis , Hypophosphatemia/physiopathology , Male , Middle Aged , Osteomalacia/blood , Osteomalacia/diagnosis , Osteomalacia/physiopathology , Phosphorus/blood , Predictive Value of Tests , Retrospective Studies , Reverse Transcriptase Inhibitors/adverse effects , Risk Factors , Time FactorsABSTRACT
Wolfram syndrome (WFS) is a rare autosomal recessive disease with non-autoimmune childhood onset insulin dependent diabetes and optic atrophy. WFS type 2 (WFS2) differs from WFS type 1 (WFS1) with upper intestinal ulcers, bleeding tendency and the lack ofdiabetes insipidus. Li-fespan is short due to related comorbidities. Only a few familieshave been reported with this syndrome with the CISD2 mutation. Here we report two siblings with a clinical diagnosis of WFS2, previously misdiagnosed with type 1 diabetes mellitus and diabetic retinopathy-related blindness. We report possible additional clinical and laboratory findings that have not been pre-viously reported, such as asymptomatic hypoparathyroidism, osteomalacia, growth hormone (GH) deficiency and hepatomegaly. Even though not a requirement for the diagnosis of WFS2 currently, our case series confirm hypogonadotropic hypogonadism to be also a feature of this syndrome, as reported before.
Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/etiology , Hypogonadism/physiopathology , Hypoparathyroidism/physiopathology , Osteomalacia/physiopathology , Wolfram Syndrome/complications , Wolfram Syndrome/physiopathology , Adolescent , Antidiuretic Agents/therapeutic use , Child , Female , Humans , Hypogonadism/genetics , Hypoparathyroidism/genetics , Insulin/therapeutic use , Male , Osteomalacia/genetics , Treatment Outcome , Wolfram Syndrome/genetics , Young AdultABSTRACT
Ezrin/radixin/moesin (ERM) proteins function as general cross-linkers between plasma membrane proteins and the actin cytoskeleton and are involved in the functional expression of membrane proteins on the cell surface. They also integrate Rho guanosine 5'-triphosphatase (GTPase) signaling to regulate cytoskeletal organization by sequestering Rho-related proteins. They act as protein kinase A (PKA)-anchoring proteins and sequester PKA close to its target proteins for their effective phosphorylation and functional regulation. Therefore, ERM proteins seem to play important roles in the membrane transport of electrolytes by ion channels and transporters. In this review, we focus on the pathophysiological roles of ERM proteins in in vivo studies and introduce the phenotypes of their knockout and knockdown mice.
Subject(s)
Cytoskeletal Proteins/metabolism , Membrane Proteins/metabolism , Microfilament Proteins/metabolism , Animals , Cell Membrane/metabolism , Cell Membrane/pathology , Cholestasis/genetics , Cholestasis/metabolism , Cholestasis/physiopathology , Cytoskeletal Proteins/deficiency , Cytoskeletal Proteins/genetics , Humans , Membrane Proteins/deficiency , Membrane Proteins/genetics , Mice , Mice, Knockout , Microfilament Proteins/deficiency , Microfilament Proteins/genetics , Osteomalacia/genetics , Osteomalacia/metabolism , Osteomalacia/physiopathology , Protein Transport/physiology , Tissue Distribution/physiology , rho-Associated Kinases/metabolismABSTRACT
Diagnostic delay of tumor induced osteomalacia (TIO) is common in clinic practice. To investigate the diagnostic condition of TIO in China and raise clinicians' awareness of TIO, we retrospectively analyzed clinical manifestations, biochemical features, and specially evaluated missed diagnoses and misdiagnoses among 144 TIO patients from Peking Union Medical College Hospital during December 1982 to December 2014. Clinical presentations of TIO mainly included bone pain, difficulty in walking, pathological fractures, muscle weakness, and height loss. TIO patients demonstrated hypophosphatemia (0.48±0.13 mmol/L), elevated serum alkaline phosphatase (277.9±152.6 U/L), reduced tubular maximum for phosphorus/glomerular filtration rate (0.39±0.14) and markedly elevated serum fibroblast growth factor 23 (FGF23) (median level 302.9 pg/mL). The average time from onset to a correct diagnosis was 2.9±2.3 years while the mean duration from onset to tumor resection was 5.4±4.2 years. The initial misdiagnosis rate was 95.1% (137/144) and 240 case-times of misdiagnoses occurred among the 144 cases. The most frequent misdiagnoses were intervertebral disc herniation, spondyloarthritis (including ankylosing spondylitis) and osteoporosis. A total of 43.1% (62/144) cases with hypophosphatemia presented on their laboratory sheets were neglected and missed diagnosed. Our study showed that TIO was frequently misdiagnosed and missed diagnosed due to its rarity, insidious onset, nonspecific clinical manifestations and clinicians' poor recognition. It is necessary to test serum phosphorus in patients with musculoskeletal symptoms and difficulty in walking. The measurement of serum FGF23 is rather valuable. Once hypophosphatemia is discovered, TIO should be suspected and it is highly recommended to search for tumors and perform curative surgery.
Subject(s)
Neoplasms, Connective Tissue/diagnosis , Beijing , Biomarkers/blood , Cohort Studies , Diagnosis, Differential , Diagnostic Errors , Female , Fibroblast Growth Factor-23 , Fibroblast Growth Factors/blood , Hospitals, Teaching , Humans , Hypophosphatemia/blood , Hypophosphatemia/etiology , Hypophosphatemia/physiopathology , Intervertebral Disc Displacement/blood , Intervertebral Disc Displacement/diagnosis , Intervertebral Disc Displacement/diagnostic imaging , Intervertebral Disc Displacement/physiopathology , Male , Medical Records , Neoplasms, Connective Tissue/blood , Neoplasms, Connective Tissue/diagnostic imaging , Neoplasms, Connective Tissue/physiopathology , Osteomalacia/blood , Osteomalacia/diagnosis , Osteomalacia/diagnostic imaging , Osteomalacia/physiopathology , Osteoporosis/blood , Osteoporosis/diagnosis , Osteoporosis/diagnostic imaging , Osteoporosis/physiopathology , Paraneoplastic Syndromes , Retrospective Studies , Spondylitis, Ankylosing/blood , Spondylitis, Ankylosing/diagnosis , Spondylitis, Ankylosing/diagnostic imaging , Spondylitis, Ankylosing/physiopathologySubject(s)
Muscle Weakness/etiology , Osteomalacia/etiology , Pelvic Bones , Vitamin D Deficiency/complications , Adult , Diagnosis, Differential , Dietary Supplements , Disease Progression , Female , Gait , Humans , Muscle Strength , Muscle Weakness/diagnosis , Muscle Weakness/drug therapy , Muscle Weakness/physiopathology , Osteomalacia/diagnostic imaging , Osteomalacia/drug therapy , Osteomalacia/physiopathology , Pelvic Bones/diagnostic imaging , Predictive Value of Tests , Severity of Illness Index , Treatment Outcome , Vitamin D/therapeutic use , Vitamin D Deficiency/diagnosis , Vitamin D Deficiency/drug therapyABSTRACT
About 150,000 people are HIV-positive in France, and the number of new cases is estimated at 7000-8000 per year, with no tendency to diminish over time. Admissions of HIV-positive patients have been decreasing, in contrast, since 2008, reflecting the dramatic improvements in quality of life and survival provided by triple antiretroviral regimens. HIV infection is now a chronic disease that exposes patients to the virus and antiretroviral drugs for many years. One consequence has been the emergence of new health conditions in HIV-positive patients, such as tumors, cardiovascular disease, and osteoarticular complications. These epidemiological and clinical changes have made it necessary for rheumatologists to learn about the osteoarticular abnormalities associated with the HIV, which they are likely to encounter at some point during their everyday practice. Osteoporosis is one such abnormality, and this review article starts with a discussion of the literature on this topic. Bone loss is common, chiefly in males. Multiple factors are involved. Studies have demonstrated an increase in the fracture risk and, consequently, recommendations about the screening and treatment of osteoporosis have been issued. The focus of this review article then turns to the other rheumatic manifestations seen in HIV-positive patients, including osteomalacia, avascular necrosis, and inflammatory joint disease. Osteoarticular pain is frequently reported by HIV-positive patients. Identifying the cause is essential to determine the best treatment strategy. Interestingly, immunosuppressant drugs, and even biotherapies, have shown a good safety profile in these immunodeficient patients.
Subject(s)
HIV Infections/drug therapy , HIV Infections/epidemiology , Rheumatic Diseases/epidemiology , Rheumatic Diseases/physiopathology , Antiretroviral Therapy, Highly Active/methods , Arthritis, Infectious/epidemiology , Arthritis, Infectious/physiopathology , Arthritis, Rheumatoid/epidemiology , Arthritis, Rheumatoid/physiopathology , Comorbidity , Female , HIV Infections/diagnosis , Humans , Incidence , Male , Osteomalacia/epidemiology , Osteomalacia/physiopathology , Osteonecrosis/epidemiology , Osteonecrosis/physiopathology , Osteoporosis/epidemiology , Osteoporosis/physiopathology , PrognosisABSTRACT
In Fanconi syndrome, hypophosphatemic osteomalacia is caused by proximal renal tubule dysfunction which leads to impaired reabsorption of amino acids, glucose, urate, and phosphate. We present a rare case of a 43-year-old Korean male who was found to have insufficiency stress fracture of the femoral neck secondary to osteomalacia due to Fanconi syndrome. He had been receiving low-dose adefovir dipivoxil (ADV, 10 mg/day) for the treatment of chronic hepatitis B virus infection for 7 years and he subsequently developed severe hypophosphatemia and proximal renal tubule dysfunction. The incomplete femoral neck fracture was fixed with multiple cannulated screws to prevent further displacement of the initial fracture. After cessation of ADV and correction of hypophosphatemia with oral phosphorus supplementation, the patient's clinical symptoms, such as bone pain, muscle weakness, and laboratory findings improved.
Subject(s)
Adenine/analogs & derivatives , Antiviral Agents/adverse effects , Fanconi Syndrome , Femoral Neck Fractures , Fractures, Spontaneous , Hepatitis B, Chronic/drug therapy , Organophosphonates/adverse effects , Osteomalacia , Adenine/adverse effects , Adenine/therapeutic use , Adult , Antiviral Agents/therapeutic use , Fanconi Syndrome/chemically induced , Fanconi Syndrome/complications , Femoral Neck Fractures/diagnostic imaging , Femoral Neck Fractures/etiology , Femoral Neck Fractures/physiopathology , Femoral Neck Fractures/therapy , Fractures, Spontaneous/diagnostic imaging , Fractures, Spontaneous/etiology , Fractures, Spontaneous/physiopathology , Fractures, Spontaneous/therapy , Humans , Male , Organophosphonates/therapeutic use , Osteomalacia/diagnostic imaging , Osteomalacia/etiology , Osteomalacia/physiopathology , Osteomalacia/therapyABSTRACT
Hypophosphatasia is a genetic disorder, characterised by a dysfunctional tissue-non-specific isoenzyme of alkaline phosphatase that impacts bone metabolism and predisposes to osteomalacia or rickets. The clinical presentation is very diverse, depending on the age of onset and the severity of the disease. Several forms of hypophosphatasia are recognised. We present a case of a 50-year-old woman with low impact fractures and loss of teeth at a young age. She also had a low alkaline phosphatase and was diagnosed with adult hypophosphatasia. Although the severe forms of hypophosphatasia are rather rare, the adult form is thought to occur quite frequently. As this condition is not well known by healthcare professionals, the time to diagnosis and initiation of adequate treatment is often postponed. When encountering a patient with low alkaline phosphatase, low bone density or a history of bone fractures, the possibility of hypophosphatasia should be considered.
Subject(s)
Alkaline Phosphatase/blood , Dietary Supplements , Fractures, Bone/etiology , Fractures, Spontaneous/etiology , Hypophosphatasia/diagnosis , Osteomalacia/diagnosis , Alkaline Phosphatase/genetics , Bone Density Conservation Agents/administration & dosage , Calcium/administration & dosage , DNA Mutational Analysis , Female , Fractures, Bone/prevention & control , Fractures, Spontaneous/prevention & control , Humans , Hypophosphatasia/blood , Hypophosphatasia/genetics , Hypophosphatasia/physiopathology , Middle Aged , Mutation, Missense , Osteomalacia/blood , Osteomalacia/physiopathology , Treatment Outcome , Vitamin D/administration & dosage , Vitamin D Deficiency/drug therapyABSTRACT
Substantial advances have been made in the past two decades in the management of osteoporosis. However, none of the current medications can eliminate the risk of fracture and rejuvenate the skeleton. To this end, we recently reported that transplantation of hematopoietic stem/progenitor cells (HSCs) or Sca1(+) cells engineered to overexpress FGF2 results in a significant increase in lamellar bone matrix formation at the endosteum; but this increase was attended by the development of secondary hyperparathyroidism and severe osteomalacia. Here we switch the therapeutic gene to PDGFB, another potent mitogen for mesenchymal stem cells (MSCs) but potentially safer than FGF2. We found that modest overexpression of PDGFB using a relatively weak phosphoglycerate kinase (PGK) promoter completely avoided osteomalacia and secondary hyperparathyroidism, and simultaneously increased trabecular bone formation and trabecular connectivity, and decreased cortical porosity. These effects led to a 45% increase in the bone strength. Transplantation of PGK-PDGFB-transduced Sca1(+) cells increased MSC proliferation, raising the possibility that PDGF-BB enhances expansion of MSC in the vicinity of the hematopoietic niche where the osteogenic milieu propels the differentiation of MSCs toward an osteogenic destination. Our therapy should have potential clinical applications for patients undergoing HSC transplantation, who are at high risk for osteoporosis and bone fractures after total body irradiation preconditioning. It could eventually have wider application once the therapy can be applied without the preconditioning.
Subject(s)
Bone and Bones/physiopathology , Genetic Therapy , Hematopoietic Stem Cell Transplantation , Proto-Oncogene Proteins c-sis/genetics , Proto-Oncogene Proteins c-sis/therapeutic use , Alkaline Phosphatase/blood , Animals , Antigens, Ly/metabolism , Body Weight , Bone Remodeling , Cell Differentiation , Cell Proliferation , Hyperparathyroidism/complications , Hyperparathyroidism/metabolism , Hyperparathyroidism/physiopathology , Hyperparathyroidism/therapy , Ki-67 Antigen/metabolism , Lentivirus/metabolism , Membrane Proteins/metabolism , Mesenchymal Stem Cells/cytology , Mice , Models, Biological , Neovascularization, Physiologic , Osteoblasts/metabolism , Osteoblasts/pathology , Osteocalcin/blood , Osteogenesis , Osteomalacia/complications , Osteomalacia/physiopathology , Phosphoglycerate Kinase/genetics , Phosphoglycerate Kinase/metabolism , Promoter Regions, Genetic/genetics , Spleen Focus-Forming Viruses/metabolism , Transduction, Genetic , Transgenes , Weight-BearingABSTRACT
The recent trends in avoiding sunbathing and eating fewer fish products have resulted in a high prevalence of vitamin D deficiency in the general Japanese population. We herein report the case of a young woman with enduring anorexia nervosa (AN) who suffered from osteomalacia, thoracic deformities and respiratory failure. Her vitamin D deficiency had been overlooked for years. Although the serum 25-hyroxyvitamin D [25(OH)D] level is a marker of vitamin D stores, it is not routinely examined because the cost is not covered by the national health insurance program. However, measuring the serum 25(OH)D levels in AN patients with hypocalcemia is recommended to prevent osteomalacia and osteoporosis.
Subject(s)
Anorexia Nervosa/complications , Bone Density Conservation Agents/therapeutic use , Calcium Compounds/therapeutic use , Hydroxycholecalciferols/therapeutic use , Lactates/therapeutic use , Osteomalacia/etiology , Respiratory Insufficiency/etiology , Vitamin D Deficiency/complications , Adult , Anorexia Nervosa/metabolism , Anorexia Nervosa/physiopathology , Female , Humans , Osteomalacia/drug therapy , Osteomalacia/metabolism , Osteomalacia/physiopathology , Prevalence , Respiratory Insufficiency/physiopathology , Treatment Outcome , Vitamin D/blood , Vitamin D Deficiency/bloodABSTRACT
Fibroblast growth factor-23 (FGF23) regulates phosphate reabsorption in the kidney and therefore plays an essential role in phosphate balance in humans. There is a host of defects that ultimately lead to excess FGF23 levels and thereby cause renal phosphate wasting and hypophosphatemic rickets. We describe the genetic, pathophysiologic, and clinical aspects of this group of disorders with a focus on X-linked hypophosphatemia (XLH), the best characterized of these abnormalities. We also discuss autosomal dominant hypophosphatemic rickets (ADHR), autosomal recessive hypophosphatemic rickets (ARHR) and tumor-induced osteomalacia (TIO) in addition to other rarer FGF23-mediated conditions. We contrast the FGF23-mediated disorders with FGF23-independent hypophosphatemia, specifically hypophosphatemic rickets with hypercalciuria (HHRH). Errant diagnosis of hypophosphatemic disorders is common. This review aims to enhance the recognition and appropriate diagnosis of hypophosphatemia and to guide appropriate treatment.
Subject(s)
Fibroblast Growth Factors/physiology , Homeostasis/physiology , Phosphorus/metabolism , Rickets, Hypophosphatemic/physiopathology , Bone and Bones/metabolism , Calcitonin/therapeutic use , Fibroblast Growth Factor-23 , Humans , Osteomalacia/physiopathology , Rickets, Hypophosphatemic/diagnosis , Rickets, Hypophosphatemic/geneticsSubject(s)
Brain Neoplasms/pathology , Brain/pathology , Hemangiopericytoma/pathology , Intracranial Hemorrhages/pathology , Lipoma/pathology , Osteomalacia/pathology , Rectal Neoplasms/pathology , Adult , Brain/surgery , Brain Neoplasms/physiopathology , Cerebral Angiography , Female , Hemangiopericytoma/physiopathology , Humans , Intracranial Hemorrhages/physiopathology , Lipoma/physiopathology , Magnetic Resonance Imaging , Osteomalacia/physiopathology , Rectal Neoplasms/physiopathologySubject(s)
Hemangiopericytoma/complications , Hypophosphatemia/etiology , Osteomalacia/etiology , Thoracic Neoplasms/complications , Aged , Chronic Disease , Fibroblast Growth Factor-23 , Fibroblast Growth Factors/metabolism , Hemangiopericytoma/metabolism , Humans , Hypophosphatemia/physiopathology , Male , Osteomalacia/physiopathology , Thoracic Neoplasms/metabolismABSTRACT
Osteomalacia is a rare disorder of bone metabolism leading to reduced bone mineralization. Underlying vitamin D deficiency and a disturbed phosphate metabolism (so-called hypophosphatemic osteomalacia) can cause the disease. Leading symptoms are dull localized or generalized bone pain, muscle weakness and cramps as well as increased incidence of falls. Rheumatic diseases, such as polymyalgia rheumatica, rheumatoid arthritis, myositis and fibromyalgia must be considered in the differential diagnosis. Alkaline phosphatase (AP) is typically elevated in osteomalacia while serum phosphate and/or 25-OH vitamin D3 levels are reduced. The diagnosis of osteomalacia can be confirmed by an iliac crest bone biopsy. Histological correlate is reduced or deficient mineralization of the newly synthesized extracellular matrix. Treatment strategies comprise supplementation of vitamin D and calcium and for patients with intestinal malabsorption syndromes vitamin D and calcium are also given parenterally. In renal phosphate wasting syndromes substitution of phosphate is the treatment of choice, except for tumor-induced osteomalacia when removal of the tumor leads to a cure in most cases.
Subject(s)
Bone Density/physiology , Bone and Bones/physiopathology , Osteoarthritis/physiopathology , Alkaline Phosphatase/physiology , Bone Density/drug effects , Bone and Bones/drug effects , Calcium/therapeutic use , Humans , Osteoarthritis/diagnosis , Osteoarthritis/drug therapy , Osteomalacia/diagnosis , Osteomalacia/drug therapy , Osteomalacia/physiopathology , Paraneoplastic Syndromes/diagnosis , Paraneoplastic Syndromes/drug therapy , Paraneoplastic Syndromes/physiopathology , Rickets, Hypophosphatemic/diagnosis , Rickets, Hypophosphatemic/drug therapy , Rickets, Hypophosphatemic/physiopathology , Vitamin D/therapeutic use , Vitamin D Deficiency/drug therapy , Vitamin D Deficiency/physiopathologyABSTRACT
No disponible
Subject(s)
Humans , Fibroblast Growth Factors/physiology , Skeleton , Musculoskeletal Physiological Phenomena , Osteomalacia/physiopathologyABSTRACT
Fundamento y objetivo: El objetivo de este estudio ha sido analizar la utilidad de la determinación del fibroblast growth factor 23 (FGF23, «factor de crecimiento de los fibroblastos 23»), una hormona reguladora del metabolismo del fosfato, en la valoración de pacientes con osteomalacia de distintas causas. Pacientes y método: Se incluyeron 17 pacientes con osteomalacia: 12 hipofosfatémica (de distintas causas), 4 por déficit de vitamina D y uno por hipofosfatasia. En todos ellos se determinó el FGF23 C -terminal plasmático. Resultados: Se observó un aumento del FGF23 en 6/12 (50%) pacientes con osteomalacia hipofosfatémica (2 ligada a cromosoma X , una autosómica dominante, una asociada a tratamiento por VIH y 2 no filiadas). Ningún paciente con osteomalacia por déficit de vitamina D o hipofosfatasia presentó un aumento del FGF23. Conclusión: La determinación del FGF23 puede ser útil en la valoración de los distintos tipos de osteomalacia hipofosfatémica y en la identificación del mecanismo etiopatogénico asociado. Así, el 50% de los pacientes con osteomalacia hipofosfatémica, dependiendo de su etiología, tienen un aumento de FGF23, mientras que en la osteomalacia por déficit de vitamina D y en la hipofosfatasia los valores de esta hormona son normales
Background and objective The aim of the present study was to analyze the usefulness of the determination of fibroblast growth factor 23 (FGF23), a regulatory hormone of phosphate metabolism, in the evaluation of patients with osteomalacia of different causes. Patients and method Seventeen patients with osteomalacia were included: 12 hypophosphatemic osteomalacia (by several causes), 4 vitamin D-deficiency osteomalacia and one with hypophosphatasia. Plasma C-terminal FGF23 was determined in all patients. Results FGF23 levels were increased in 6/12 (50%) of patients with hypophosphatemic osteomalacia (2 X -linked, one autosomal dominant, one related HIV therapy and 2 not elucidated). No patient with vitamin D-deficiency osteomalacia or hypophosphatasia presented increased FGF23 levels. Conclusion The determination of FGF23 could be useful in the evaluation of the different types of hypophosphatemic osteomalacia and also in the identification of their associated etiopathogenic mechanisms. Thus, depending on the cause, 50% of the patients with hypophosphatemic osteomalacia showed increased FGF23 values, whereas in vitamin D-deficiency osteomalacia and in hypophosphatasia FGF23 levels were normal (AU)
Subject(s)
Humans , Osteomalacia/physiopathology , Fibroblast Growth Factors/physiology , Hypophosphatemia/physiopathology , Phosphates/metabolism , Vitamin D Deficiency/physiopathologyABSTRACT
Bilateral femoral neck insufficiency fracture due to osteomalacia in pregnancy is an extremely rare condition. In this article, we report a 22-year-old female case with bilateral femoral neck fractures in whom the diagnosis was delayed due to the avoidance of ionising radiation and managing hip complaints by conservatively in pregnancy. She was treated surgically with internal fixation using cannulated screws and received medical treatment for vitamin D deficiency.
Subject(s)
Calcium Compounds/administration & dosage , Cholecalciferol/administration & dosage , Femoral Neck Fractures , Fracture Fixation, Internal/methods , Fractures, Stress , Osteomalacia , Pregnancy Complications , Vitamin D Deficiency/complications , Adult , Bone Density Conservation Agents/administration & dosage , Delayed Diagnosis , Female , Femoral Neck Fractures/diagnosis , Femoral Neck Fractures/etiology , Femoral Neck Fractures/physiopathology , Femoral Neck Fractures/surgery , Femur Neck/pathology , Fractures, Stress/diagnosis , Fractures, Stress/etiology , Fractures, Stress/physiopathology , Fractures, Stress/surgery , Humans , Magnetic Resonance Imaging , Osteomalacia/diagnosis , Osteomalacia/drug therapy , Osteomalacia/etiology , Osteomalacia/physiopathology , Osteomalacia/surgery , Pregnancy , Pregnancy Complications/diagnosis , Pregnancy Complications/drug therapy , Pregnancy Complications/etiology , Pregnancy Complications/physiopathology , Pregnancy Complications/surgery , Treatment Outcome , Vitamin D Deficiency/blood , Vitamin D Deficiency/diagnosisABSTRACT
Celiac disease (CD), a malabsorption syndrome caused by hypersensitivity to gliadin fraction of gluten. CD can manifest with classic symptoms; however, significant myopathy and multiple fractures are rarely the predominant presentation of untreated celiac disease. Osteomalacia complicating celiac disease had become more and more rare. We describe here a case of osteomalacia secondary to a longstanding untreated celiac disease. This patient complained about progressive bone and muscular pain, weakness, fractures and skeletal deformities. Radiological and laboratory findings were all in favor of severe osteomalacia. Improvement of patient's weakness and laboratory abnormalities was obvious after treatment with gluten free diet, vitamin D, calcium and iron. This case affirms that chronic untreated celiac disease, can lead to an important bone loss and irreversible complications like skeletal deformities.