DOCSLIB.ORG

Tumor-Induced Osteomalacia

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Tumor-Induced Osteomalacia Downloaded from www.jama.com at Johns Hopkins University, on November 23, 2005 GRAND ROUNDS CLINICIAN’S CORNER AT THE JOHNS HOPKINS BAYVIEW MEDICAL CENTER Tumor-Induced Osteomalacia Suzanne M. Jan de Beur, MD Tumor-induced osteomalacia (TIO) is a rare paraneoplastic form of renal phos- CASE PRESENTATION phate wasting that results in severe hypophosphatemia, a defect in vitamin D Ms R, who is 55 years old, developed a metabolism, and osteomalacia. This debilitating disorder is illustrated by the rare disorder nearly 20 years ago that clinical presentation of a 55-year-old woman with progressive fatigue, weak- initially went undiagnosed for more ness, and muscle and bone pain with fractures. After a protracted clinical course than a year despite numerous physi- and extensive laboratory evaluation, tumor-induced osteomalacia was iden- cian visits. Since her initial diagnosis, tified as the basis of her clinical presentation. In this article, the distinctive Ms R receives medical therapy that has clinical characteristics of this syndrome, the advances in diagnosis of TIO, and improved her symptoms; however, de- finitive therapy has been thwarted be- new insights into the pathophysiology of this disorder are discussed. cause the tumor causing her illness re- JAMA. 2005;294:1260-1267 www.jama.com mains obscure. DR JAN DE BEUR: Back in 1984, nists at 2 different institutions, a psy- care for them and for myself. Now, it is when you had onset of this disorder, chiatrist, and a family practitioner. I was frustrating to know the diagnosis but not what difficulties were you experienc- hospitalized for several days but the be able to definitively treat it. ing at that time? evaluation was unrevealing. DR JAN DE BEUR: Do you have any- MS R: Initially, I experienced pain on DR JAN DE BEUR: What was the ini- one in your immediate or extended fam- the bottom of my right foot that quickly tial finding that suggested your diag- ily with similar symptoms, unex- progressed to pain in both feet. Within nosis? plained broken bones, short stature, a month, the pain had progressed to my MS R: I saw a rheumatologist at an bowed legs, or low blood phosphorus? whole body and had intensified in academic medical center who discov- MS R: No—both my sons are alive severity. ered that I had a low blood phospho- and well and more than 6 feet tall. There DR JAN DE BEUR: What happened rus level. is no one else with low blood phospho- when you began seeking medical at- DR JAN DE BEUR: What were you rus. My sister and brother are alive and tention? treated with and how did you respond well, with normal height and normal MS R: The initial diagnosis was to treatment? blood phosphorus. “fallen arches.” Then I was told that the MS R: Initially, I was treated with At 37 years of age, Ms R presented excruciating muscle weakness and pain phosphorus alone. Despite this treat- with abrupt onset of profound fatigue I was experiencing was stress-related. ment, the fractures I had sustained in accompanied by bone pain that be- When I persisted, some blood work was my ribs and pelvis were not healing, my came progressive and debilitating. She sent but I was told that the blood work blood phosphorus was not improving, sought medical attention but was told was “normal.” At one point, when I be- and my severe pain persisted. Once cal- that her symptoms were psychologi- came so debilitated and weak that I was citriol was added to the phosphorus, my cal, and at one point, was diagnosed as unable to function well in my daily ac- symptoms improved substantially having conversion disorder. Still undi- tivities, I was given the diagnosis of con- within 6 months. agnosed, she experienced rib and pel- version disorder. DR JAN DE BEUR: What has been the vic fractures. Finally, after more than DR JAN DE BEUR: How long did it take most difficult part of living with this rare disorder? Author Affiliation: Department of Medicine, Johns before a diagnosis was made? Hopkins University School of Medicine, and Depart- MS R: Close to a year. I sought medi- MS R: Initially, not knowing what was ment of Endocrinology, Johns Hopkins Bayview Medi- wrong with me and why I was in so cal Center, Baltimore, Md. cal attention from a podiatrist, inter- Corresponding Author: Suzanne M. Jan de Beur, MD, much pain. I wondered if I was losing Johns Hopkins University School of Medicine, Johns my mind. I had the sole responsibility Hopkins Bayview Medical Center, 4940 Eastern Ave, CME available online at for 2 children and I could not function B114, Baltimore, MD 21224 ([email protected]). www.jama.com Grand Rounds Section Editor: David S. Cooper, MD, well. I was worried about being able to Contributing Editor, JAMA. 1260 JAMA, September 14, 2005—Vol 294, No. 10 (Reprinted) ©2005 American Medical Association. All rights reserved. Downloaded from www.jama.com at Johns Hopkins University, on November 23, 2005 TUMOR-INDUCED OSTEOMALACIA a year, an astute physician recognized 1.1 mg/dL (97 µmol/L), a low phos- mia stimulates calcitriol synthesis via the connection between her low se- phorus level of 1.2 mg/dL (0.36 mmol/ 25-hydroxyvitamin D–1␣-hydroxy- rum phosphorus levels and her pro- L)(normal range, 2.5-4.5 mg/dL [0.81- lase in the kidney, leading to in- found fatigue, weakness, bone pain, and 1.45 mmol/L]), an elevated alkaline creased calcium and phosphorus ab- fractures, and she was diagnosed as hav- phosphatase level of 137 U/L (normal sorption in the intestine and enhanced ing osteomalacia. Medical therapy was range, 30-120 U/L), and an inappro- mobilization of calcium and phospho- initiated with oral phosphorus alone, priately low 1,25-dihydroxyvitamin D rus from bone (FIGURE 1). The result- with little improvement, then cal- level of less than 5 pg/mL (normal ant increased serum calcium and in- citriol was added and significant im- range, 9-52 pg/mL). Her tubular reab- creased calcitriol inhibit PTH secretion, provement in her symptoms followed. sorption of phosphate was very low at with a subsequent increase in urinary It was upon transferring her care when 10% (normal range, 78%-98%), indi- calcium excretion and increased tubu- she moved to Baltimore, Md (more than cating renal phosphate wasting. Her 25- lar reabsorption of phosphorus. Thus, 10 years after her original diagnosis) hydroxyvitamin D level was normal. normal serum calcium levels are main- that the diagnosis was refined from os- Her intact parathyroid hormone (PTH) tained and serum phosphorus levels teomalacia to tumor-induced osteoma- level, which was reportedly normal be- are returned to normal. In addition, hy- lacia (TIO). The distinguishing clini- fore initiation of therapy, was elevated pophosphatemia is a potent stimula- cal features that suggested TIO were the at 124 pg/mL (normal range, 10-65 pg/ tor of renal tubular reabsorption of presence of renal phosphate wasting mL) when she was evaluated in Balti- phosphate. and an inappropriately low 1,25- more, after she had been treated for sev- The kidney is the principal organ that dihydroxyvitamin D level before treat- eral years. Fibroblast growth factor 23 regulates phosphate homeostasis. Se- ment with calcitriol. In an effort to lo- (FGF-23) levels measured during treat- rum inorganic phosphorus is filtered by cate and remove the causative tumor, ment were markedly elevated at 3768 the glomerulus and 80% of the filtered Ms R has endured a series of disap- relative units/mL (normal range, 0-150 load is reabsorbed predominantly along pointing tumor localization proce- relative units/mL). Of note, Ms R had the proximal nephron. Regulation of dures and has had complications of the previously documented normal se- proximal renal tubular reabsorption of medical therapy for TIO. Extensive im- rum phosphorus levels. phosphate is achieved through changes aging, including octreotide scanning, in the activity, number, and intracel- has been unrevealing in locating the DISCUSSION lular location of the brush border mem- causative tumor. In pursuit of the tu- Ms R’s case is instructive for 2 rea- brane type IIa sodium-phosphate co- mor, she has undergone 2 surger- sons: first, it shows that an internist transporter (NaPiIIa). ies—1 to remove a suspected sinus tu- should consider TIO in any patient with Parathyroid hormone is the best- mor and 1 to remove a suspected tumor persistent, enigmatic bone pain accom- characterized physiological regulator of near her thyroid. Neither surgery panied by low serum phosphorus lev- phosphorus reabsorption, but its prin- yielded the causative tumor or led to els. Second, basic investigation of TIO cipal function is to maintain calcium the remission of the biochemical mani- is providing exciting breakthroughs in homeostasis. Parathyroid hormone in- festations of TIO. Ms R has experi- understanding of the pathogenesis of creases urinary phosphate excretion via enced complications of long-term treat- TIO and other metabolic disorders of cyclic adenosine monophosphate– ment with phosphorus and calcitriol; phosphate homeostasis. dependent inhibition of NaPiIIa expres- she has developed both nephrolithia- sion. This effect is rapid and is achieved Phosphate Homeostasis: sis and tertiary hyperparathyroidism. by internalization of NaPiIIa transport- Currently, the location of Ms R’s tu- Current Understanding ers from the brush border membrane mor is unknown. Phosphorus is a critical element in skel- and enhanced lysosomal degradation. On physical examination, her vital etal development, bone mineralization, However, this classic PTH–vitamin D signs are normal; her height is 66 in. Her membrane composition (phospholip- axis does not account for all the com- physical examination results are normal. ids), nucleotide structure (adenosine tri- plexities of phosphate homeostasis, and In particular, she has no bowed legs or phosphate, which provides energy and the study of renal phosphate-wasting sequelae of rickets.
Load more

Recommended publications
  • Causes of Short Stature Author Alan D Rogol, MD, Phd Section Editors
    Causes of short stature Author Alan D Rogol, MD, PhD Section Editors Peter J Snyder, MD Mitchell Geffner, MD Deputy Editor Alison G Hoppin, MD Contributor disclosures All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Mar 2016. | This topic last updated: Aug 13, 2015. INTRODUCTION — Short stature is a term applied to a child whose height is 2 standard deviations (SD) or more below the mean for children of that sex and chronologic age (and ideally of the same racial-ethnic group). This corresponds to a height that is below the 2.3rd percentile. Short stature may be either a variant of normal growth or caused by a disease. The most common causes of short stature beyond the first year or two of life are familial (genetic) short stature and delayed (constitutional) growth, which are normal non-pathologic variants of growth. The goal of the evaluation of a child with short stature is to identify the subset of children with pathologic causes (such as Turner syndrome, inflammatory bowel disease or other underlying systemic disease, or growth hormone deficiency). The evaluation also assesses the severity of the short stature and likely growth trajectory, to facilitate decisions about intervention, if appropriate. This topic will review the main causes of short stature. The diagnostic approach to children with short stature is discussed separately. (See "Diagnostic approach to children and adolescents with short stature".) NORMAL VARIANTS OF GROWTH Familial short stature — Familial or genetic short stature is most often a normal variant, termed familial or genetic short stature (figure 1).
    [Show full text]
  • Hypophosphatasia Could Explain Some Atypical Femur Fractures
    Hypophosphatasia Could Explain Some Atypical Femur Fractures What we know Hypophosphatasia (HPP) is a rare genetic disease that affects the development of bones and teeth in children (Whyte 1985). HPP is caused by the absence or reduced amount of an enzyme called tissue-nonspecific alkaline phosphatase (TAP), also called bone-specific alkaline phosphatase (BSAP). The absence of TAP raises the level of inorganic pyrophosphate (Pi), which prevents calcium and phosphate from creating strong, mineralized bone. Without TAP, bones can become weak. In its severe form, HPP is fatal and happens in 1/100,000 births. Because HPP is genetic, it can appear in adults as well. A recent study has identified a milder, more common form of HPP that occurs in 4 of 1000 adults (Dahir 2018). This form of HPP is usually seen in early middle aged adults who have low bone density and sometimes have stress fractures in the feet or thigh bone. Sometimes these patients lose their baby teeth early, but not always. HPP is diagnosed by measuring blood levels of TAP and vitamin B6. An elevated vitamin B6 level [serum pyridoxal 5-phosphate (PLP)] (Whyte 1985) in a patient with a TAP level ≤40 or in the low end of normal can be diagnosed with HPP. Almost half of the adult patients with HPP in the large study had TAP >40, but in the lower end of the normal range (Dahir 2018). The connection between hypophosphatasia and osteoporosis Some people who have stress fractures get a bone density test and are treated with an osteoporosis medicine if their bone density results are low.
    [Show full text]
  • Effects of Tumor-Induced Osteomalacia on the Bone Mineralization Process
    Calcif Tissue Int (2009) 84:313–323 DOI 10.1007/s00223-009-9216-z Effects of Tumor-Induced Osteomalacia on the Bone Mineralization Process K. Nawrot-Wawrzyniak Æ F. Varga Æ A. Nader Æ P. Roschger Æ S. Sieghart Æ E. Zwettler Æ K. M. Roetzer Æ S. Lang Æ R. Weinkamer Æ K. Klaushofer Æ N. Fratzl-Zelman Received: 24 October 2008 / Accepted: 4 January 2009 / Published online: 14 February 2009 Ó The Author(s) 2009. This article is published with open access at Springerlink.com Abstract Fibroblast growth factor 23 (FGF23) overex- distribution using quantitative backscattered electron pression has been identified as a causative factor for tumor- imaging were performed on the bone biopsy. The data induced osteomalacia (TIO) characterized by hypophos- showed important surface osteoidosis and a slightly phatemia due to increased renal phosphate wasting, low increased osteoblast but markedly decreased osteoclast 1,25(OH)2D3 serum levels, and low bone density. The number. The mineralized bone volume (-11%) and miner- effects of long-lasting disturbed phosphate homeostasis on alized trabecular thickness (-18%) were low. The mean bone mineralization are still not well understood. We report degree of mineralization of the bone matrix (-7%), the most on a patient with a 12-year history of TIO, treated with frequent calcium concentration (-4.1%), and the amounts of 1,25(OH)2D3 and phosphate, who finally developed hyper- fully mineralized bone (-40.3%) were distinctly decreased, parathyroidism with gland hyperplasia before the tumor while the heterogeneity of mineralization (?44.5%) and the could be localized in the scapula and removed.
    [Show full text]
  • Total Serum Phosphate Levels Less Than 3.0 Mg/Dl. • Mild Hypophosp
    HYPOPHOSPHATEMIA DEFINITION: Total serum phosphate levels less than 3.0 mg/dL. Mild hypophosphatemia: 2.5-3.0 mg/dL. Moderate hypophosphatemia: 1.0-2.5 mg/dL. Severe hypophosphatemia: < 1.0 mg/dL. INCIDENCE IN CRITICAL ILLNESS: Common. ETIOLOGY: Transcellular shift: Refeeding syndrome (abrupt initiation of carbohydrate causes an insulin spike, which increases cellular phosphate uptake); exogenous administration of insulin; respiratory alkalosis. Renal loss: Diuretics; osmotic diuresis in diabetic ketoacidosis; hyperparathyroidism (primary and secondary; decreases urinary resorption of phosphate); proximal renal tubular dysfunction (Fanconi’s syndrome). Insufficient intestinal absorption: Malnutrition; phosphate-binding antacids; vitamin D deficiency; chronic diarrhea; nasogastric tube suction; malabsorption. Extreme catabolic states: Burns; trauma; sepsis. CLINICAL MANIFESTATIONS: Cardiovascular: Acute left ventricular dysfunction; reversible dilated cardiomyopathy. Hematologic: Acute hemolytic anemia; leukocyte dysfunction. Neuromuscular: Diffuse skeletal muscle weakness; rhabdomyolysis; bone demineralization; acute and chronic respiratory failure secondary to diaphragmatic weakness (impaired ventilator weaning); confusion and lethargy; gait disturbance; paresthesias. TREATMENT: It is impossible to accurately predict the exact quantity of phosphate repletion required because most phosphate is intracellular. Moderate hypophosphatemia: Oral supplementation is usually adequate (provided the gastrointestinal tract is functional).
    [Show full text]
  • Renal Phosphate Wasting Due to Tumor-Induced (Oncogenic) Osteomalacia
    Open Access Case Report DOI: 10.7759/cureus.15507 Renal Phosphate Wasting Due to Tumor-Induced (Oncogenic) Osteomalacia Eluwana A. Amaratunga 1 , Emily B. Ernst 1 , James Kamau 1 , Ragarupa Kotala 1 , Richard Snyder 1 1. Internal Medicine, St. Luke’s University Health Network, Easton, USA Corresponding author: Eluwana A. Amaratunga, [email protected] Abstract Osteomalacia is a widely prevalent bone disorder that is caused by an imbalance in body calcium and phosphate. Tumor-induced osteomalacia (TIO) is a rare form of osteomalacia that is associated with mesenchymal tumors. It is caused by overproduction of fibroblast growth factor 23 (FGF-23), a hormone involved in phosphate regulation. A 59-year-old male with a history of factor V Leiden mutation, pulmonary embolism, and deep vein thrombosis was diagnosed with oncogenic osteomalacia in 2008 following laboratory findings significant for low phosphorus and elevated FGF-23 levels. He underwent a resection of a right suprascapular notch mass with the biopsy confirming a phosphaturic mesenchymal tumor. He was maintained on oral phosphorus and calcitriol replacements with a regular follow-up with oncology and nephrology. Eight years later, the patient’s phosphorus levels started declining despite replacement. A repeat test showed FGF-23 levels once again elevated. A whole-body magnetic resonance imaging (MRI) scan showed no significant findings. The patient was continued on oral replacement therapy with a close follow-up. Two years later, urine phosphorus excretion was elevated at 2494 mg per 24 hours with low plasma phosphorus (1.2 mg/dL) and an elevated FGF-23 level of 1005 relative units (RU)/mL.
    [Show full text]
  • Establishment of a Dental Effects of Hypophosphatasia Registry Thesis
    Establishment of a Dental Effects of Hypophosphatasia Registry Thesis Presented in Partial Fulfillment of the Requirements for the Degree Master of Science in the Graduate School of The Ohio State University By Jennifer Laura Winslow, DMD Graduate Program in Dentistry The Ohio State University 2018 Thesis Committee Ann Griffen, DDS, MS, Advisor Sasigarn Bowden, MD Brian Foster, PhD Copyrighted by Jennifer Laura Winslow, D.M.D. 2018 Abstract Purpose: Hypophosphatasia (HPP) is a metabolic disease that affects development of mineralized tissues including the dentition. Early loss of primary teeth is a nearly universal finding, and although problems in the permanent dentition have been reported, findings have not been described in detail. In addition, enzyme replacement therapy is now available, but very little is known about its effects on the dentition. HPP is rare and few dental providers see many cases, so a registry is needed to collect an adequate sample to represent the range of manifestations and the dental effects of enzyme replacement therapy. Devising a way to recruit patients nationally while still meeting the IRB requirements for human subjects research presented multiple challenges. Methods: A way to recruit patients nationally while still meeting the local IRB requirements for human subjects research was devised in collaboration with our Office of Human Research. The solution included pathways for obtaining consent and transferring protected information, and required that the clinician providing the clinical data refer the patient to the study and interact with study personnel only after the patient has given permission. Data forms and a custom database application were developed. Results: The registry is established and has been successfully piloted with 2 participants, and we are now initiating wider recruitment.
    [Show full text]
  • Rickets and Osteomalacia Management )
    Rule Category: Medical ` Ref: No: 2013-MN-0010 Version Control: Version No.3.0 Effective Date: 08-02-2019 Revision Date: February 2020 Rickets and Osteomalacia Management ) Adjudication Guideline Table of content Abstract Scope Adjudication Policy Denial codes Appendices Page 1 Page 2 Page 2 Page 3 Page 3 Approved by: Daman Abstract Responsible: Medical Standards & Research For Members Related Adjudication Guidelines: None Rickets and Osteomalacia are the two disorder caused by insufficient level of vitamins D in the body. When vitamin D deficiency occurs in children is termed as rickets, whereas deficient mineralization of the growth plate in adult termed Disclaimer Osteomalacia. By accessing these Daman Adjudication Guidelines, you acknowledge that you have read and understood the terms of use set out in the disclaimer below: Rickets symptoms aches, bone pain, and sometimes enlargement occurs in The information contained in this Adjudication Guideline is intended to outline the procedures of bones at joints, such as the wrists. Fracture may occur without any known adjudication of medical claims as applied by the trauma. National Health Insurance Company – Daman PJSC (hereinafter “Daman”). The Adjudication Guideline is not intended to be comprehensive, should not be used as treatment guidelines and should only be In Osteomalacia bone pain and muscle weakness are the classical symptoms. used for the purpose of reference or guidance for adjudication procedures and shall not be construed Fractures may also take place with little or no recognized trauma. as conclusive. Daman in no way interferes with the treatment of patient and will not bear any responsibility for treatment decisions interpreted Causes of Rickets and Osteomalacia can be lack of vitamins D intake or less through Daman Adjudication Guideline.
    [Show full text]
  • Hypophosphatasia: Current Literature for Pathophysiology, Clinical Manifestations, Diagnosis, and Treatment
    Open Access Review Article DOI: 10.7759/cureus.8594 Hypophosphatasia: Current Literature for Pathophysiology, Clinical Manifestations, Diagnosis, and Treatment Abdulai Bangura 1 , Lisa Wright 2 , Thomas Shuler 2 1. Department of Research, Trinity School of Medicine, Ratho Mill, VCT 2. Department of Orthopaedics, Carilion Clinic, Roanoke, USA Corresponding author: Abdulai Bangura, [email protected] Abstract Hypophosphatasia (HPP) is a rare inherited bone disorder identified by impaired bone mineralization. There are seven subtypes of HPP mainly characterized by their age of onset. These subtypes consist of perinatal (prenatal) benign, perinatal lethal, infantile, childhood, adult, odontohypophosphatasia, and pseudohypophosphatasia. Due to limited awareness of the condition, either misdiagnosis or delayed diagnosis is common. Furthermore, the condition is frequently treated with contraindicated drugs. This literature illustrates the most recent findings on the etiology, pathophysiology, clinical manifestations, diagnosing, and treatment for HPP and its subtypes. The etiology of the disease consists of loss-of-function mutations of the ALPL gene on chromosome one, which encodes for tissue nonspecific isoenzyme of alkaline phosphatase (TNAP). A decrease of TNAP reduces inorganic phosphate (Pi) for bone mineralization and allows for an increase in inorganic pyrophosphate (PPi) and phosphorylated osteopontin (p-OPN), which further reduces bone mineralization. The combination of these processes softens bone and mediates a clinical presentation similar to rickets/osteomalacia. HPP has an additional wide range of clinical features depending on its subtype. Although a concrete diagnostic guideline has not yet been established, many studies have supported a similar method of identifying HPP. Clinical features, radiological findings, and/or biomarker levels of the disorder should raise suspicion and encourage the inclusion of HPP as a differential diagnosis.
    [Show full text]
  • Turner Syndrome (TS) Is a Genetic Disease That Affects About Physical Signs of TS May Include: 1 in Every 2,500 Female Live Births
    Notes: A Guide for Caregivers For easily accessible answers, education, and support, visit Nutropin.com or call 1-866-NUTROPIN (1-866-688-7674). 18 19 of patients with Your healthcare team is your primary source Turner Syndrome of information about your child’s treatment. Please see the accompanying full Prescribing Information, including Instructions for Use, and additional Important Safety Information througout and on pages 16-18. Models used for illustrative purposes only. Nutropin, Nutropin AQ, and NuSpin are registered trademarks, Nutropin GPS is a trademark, and NuAccess is a service mark of Genentech, Inc. © 2020 Genentech USA, Inc., 1 DNA Way, So. San Francisco, CA 94080 M-US-00005837(v1.0) 06/20 FPO Understanding Turner Syndrome What is Turner Syndrome? Turner Syndrome (TS) is a genetic disease that affects about Physical signs of TS may include: 1 in every 2,500 female live births. TS occurs when one • Short stature of a girl’s two X chromosomes is absent or incomplete. • Webbing of the neck Chromosomes are found in all cells of the human body. They contain the genes that determine the characteristics of a • Low-set, rotated ears person such as the color of hair or eyes. Every person has • Arms that turn out slightly at the elbows 22 pairs of chromosomes containing these characteristics, • Low hairline at the back of the head and one pair of sex chromosomes. • A high, arched palate in the mouth Normally cells in a female’s body contain two “X” chromosomes Biological signs of TS may include: (Fig. 1). • Underdevelopment of the ovaries In girls with TS, part or • Not reaching sexual maturity or starting all of one X chromosome a menstrual period (Fig.
    [Show full text]
  • Osteomalacia and Osteoporosis D
    Postgrad. med.J. (August 1968) 44, 621-625. Postgrad Med J: first published as 10.1136/pgmj.44.514.621 on 1 August 1968. Downloaded from Osteomalacia and osteoporosis D. B. MORGAN Department of Clinical Investigation, University ofLeeds OSTEOMALACIA and osteoporosis are still some- in osteomalacia is an increase in the alkaline times confused because both diseases lead to a phosphatase activity in the blood (SAP); there deficiency of calcium which can be detected on may also be a low serum phosphorus or a low radiographs of the skeleton. serum calcium. This lack of calcium is the only feature Our experience with the biopsy of bone is that common to the two diseases which are in all a large excess of uncalcified bone tissue (osteoid), other ways easily distinguishable. which is the classic histological feature of osteo- malacia, is only found in patients with the other Osteomalacia typical features of the disease, in particular the Osteomalacia will be discussed first, because it clinical ones (Morgan et al., 1967a). Whether or is a clearly defined disease which can be cured. not more subtle histological techniques will detect Osteomalacia is the result of an imbalance be- earlier stages of the disease remains to be seen. tween the supply of and the demand for vitamin Bone pains, muscle weakness, Looser's zones, D. The the following description of disease is raised SAP and low serum phosphate are the Protected by copyright. based on our experience of twenty-two patients most reliable aids to the diagnosis of osteomalacia, with osteomalacia after gastrectomy; there is no and approximately in that order.
    [Show full text]
  • Assessment Report
    17 September 2020 EMA/522604/2020 Corr.1 Committee for Medicinal Products for Human Use (CHMP) Assessment report Velphoro Common name: sucroferric oxyhydroxide Procedure No. EMEA/H/C/002705/X/0020/G Note Assessment report as adopted by the CHMP with all information of a commercially confidential nature deleted. Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The Netherlands Address for visits and deliveries Refer to www.ema.europa.eu/how-to-find-us An agency of the European Union Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000 © European Medicines Agency, 2021. Reproduction is authorised provided the source is acknowledged. Table of contents 1. Background information on the procedure .............................................. 6 1.1. Submission of the dossier ...................................................................................... 6 1.2. Steps taken for the assessment of the product ......................................................... 7 2. Scientific discussion ................................................................................ 8 2.1. Problem statement ............................................................................................... 8 2.1.1. Disease or condition ........................................................................................... 8 2.1.2. Epidemiology and risk factors, screening tools/prevention ...................................... 8 2.1.3. Biologic features ...............................................................................................
    [Show full text]
  • Current Dosing of Growth Hormone in Children with Growth Hormone Deficiency: How Physiologic?
    Current Dosing of Growth Hormone in Children With Growth Hormone Deficiency: How Physiologic? Margaret H. MacGillivray, MD*; Sandra L. Blethen, MD, PhD‡; John G. Buchlis, MD*; Richard R. Clopper, ScD*; David E. Sandberg, PhD*; and Thomas A. Conboy, MS* ABSTRACT. The current doses of recombinant growth ARE THE APPROVED RECOMBINANT HUMAN GH hormone (rGH) are two to three times those used in the DOSING REGIMENS PHYSIOLOGIC? pituitary growth hormone era. These rGH doses (0.025 to A standard method for determining whether hor- 0.043 mg/kg/d) are similar to or moderately greater than mone replacement is physiologic is to compare the the physiologic requirements. Growth velocity and dose of hormone administered with the amount of height gains have been shown to be greater with 0.05 that hormone produced daily in healthy persons. For mg/kg/d of rGH than with 0.025 mg/kg/d. Larger doses of human GH, this is not an easy task because of its GH and early initiation of treatment result in greater short half-life, multicompartmental distribution, and heights at the onset of puberty and greater adult heights. Earlier onset of puberty and more rapid maturation, as episodic pulsatile pattern of secretion. In addition, indicated by bone age, were not observed in children GH has a variable secretion profile that is influenced who were given 0.18 to 0.3 mg/kg/wk of rGH. The fre- by age, diurnal rhythm, sleep, stress, nutrition, body quency of adverse events is very low, but diligent sur- weight, and sex hormones. One approach to calcu- veillance of all children who are treated with rGH is lating daily levels of endogenously produced GH essential.
    [Show full text]