Treatment Of Hypophosphatemic Rickets Research Articles

The Efficacy of Burosumab Treatment for Hypophosphatemic Rickets: Systematic Review

Background/Objective: The approval of burosumab for the treatment of X-linked hypophosphatemia (XLH) in adults and children is a significant milestone. Nevertheless, there is a scarcity of data regarding its safety and efficacy in adolescents. The primary objective of this research is to assess the safety and effectiveness of burosumab in the treatment of hypophosphatemia rickets in adolescents.
 Methods: An extensive and comprehensive search was carried out primarily utilizing the PubMed database, in accordance with the PRISMA criteria. The search parameters were confined to studies conducted in the English language that investigated the effectiveness and safety of burosumab in the treatment of hypophosphatemic rickets. Specific criteria for inclusion and exclusion were established to guarantee the quality and relevance of the research under evaluation.
 Results: The study encompassed a broad spectrum of research from various geographical regions across the globe, with no particular focus on gender or age. A discernible pattern emerged, indicating a favorable efficacy of burosumab as a therapeutic intervention for hypophosphatemic rickets.
 Conclusion: Burosumab seems to enhance results in both younger and older children with hypophosphatemic rickets.

Dental manifestations and treatment of hypophosphatemic rickets: A case report and review of literature

BackgroundThe treatment and management of patients suffering from hypophosphatemic rickets (HR) remain a major challenge for dental practitioners and affected patients.ObjectivesTo report a case of HR presenting with specific dental findings and to review the dental manifestations and treatment of HR patients.MethodsCase: A 32-year-old male presented with multiple dental abscesses and short stature. A thorough history was taken followed by clinical oral examination, and relevant radiological investigation was done. Literature research: In 2020, electronic literature searches were carried out in PubMed and complemented by a careful assessment of the reference lists of the identified relevant papers. Articles and reports fulfilled the inclusion criteria: indexed reviews, case series and case reports in English and restricted to human studies were considered.ResultsThe intraoral examination revealed multiple dental abscesses and general periodontal disease; the radiographic examination showed poorly defined lamina dura, large pulp chambers and periapical lesions. Based on the contents of the 43 articles identified in the search, the current knowledge of dental manifestations, treatment and management of HR was summarized.ConclusionsAs HR is a multisystem disease, multidisciplinary care is needed. By summarizing current evidences, we proposed an evidence-based dental management and provided recommendations on diagnosis and treatment of the disease.It is of profound clinical significance to acquire knowledge of the dental manifestations and provide optimal treatment options for patients.

Nationwide Turkish Cohort Study of Hypophosphatemic Rickets

Objective:Hypophosphatemic rickets (HR) is a rare renal phosphate-wasting disorder, which is usually X-linked and is commonly caused by PHEX mutations. The treatment and follow-up of HR is challenging due to imperfect treatment options.Methods:Here we present nationwide initial and follow-up data on HR.Results:From 24 centers, 166 patients were included in the study. Genetic analysis (n=75) showed PHEX mutation in 80% of patients. The mean follow-up period was 6.7±2.4 years. During the first 3-years of treatment (n=91), mild increase in phosphate, decrease in alkaline phosphatase and elevation in parathyroid hormone (PTH) levels were detected. The height standard deviation scores were -2.38, -2.77, -2.72, -2.47 at initial, 1st, 2nd and 3rd year of treatment, respectively (p>0.05). On follow-up 36% of the patients showed complete or significant improvement in leg deformities and these patients had similar phosphate levels at presentation with better levels in 1st and 2nd years of treatment; even the treatment doses of phosphate were similar. Furthermore, 27 patients developed nephrocalcinosis (NC), the patients showed no difference in biochemical differences at presentation and follow-up, but 3rd year PTH was higher. However, higher treatment doses of phosphate and calcitriol were found in the NC group.Conclusion:HR treatment and follow-up is challenging and our results showed higher treatment doses were associated with NC without any change in serum phosphate levels, suggesting that giving higher doses led to increased phosphaturia, probably through stimulation of fibroblast growth factor 23. However, higher calcitriol doses could improve bone deformities. Safer and more efficacious therapies are needed.

Clinical Evidence for the Benefits of Burosumab Therapy for X-Linked Hypophosphatemia (XLH) and Other Conditions in Adults and Children

Burosumab (KRN23) is an FGF23 neutralizing antibody that has been the subject of several recent clinical trials principally focused on the treatment of hypophosphatemic rickets in patients with X-linked hypophosphatemia (XLH). Since the first publications in 2014, these trials have demonstrated efficacy with minimal safety concerns in both adult and pediatric cohorts. These studies have used dose-escalation to establish a dosing regimen that is well-tolerated in clinical use. This review summarizes the clinical trial data with respect to burosumab treatment in adults and children as well as noting several clinical trials currently underway. While burosumab appears transformative for the treatment of XLH, long term follow-up studies would be required to allay concerns over the potential for nephrocalcinosis and cardiac calcification. While these do not appear to be problematic in current trials, the effects of chronic or lifelong treatment have yet to be established.

New advance in hypophosphatemic rickets

Hypophosphatemic rickets(HR) is a bone mineralization disorder caused by phosphate wasting, including hypophosphatemia, bone abnormalities and short stature.X-linked hypophosphatemia(XLH) is the most common inherited disease related to phosphate metabolism, which might result in elevated levels of fibroblast growth factor 23 (FGF23). FGF23 plays an important role in the disease mechanism, so a human anti-FGF23 antibody is developed as a potential treatment for XLH.In many clinical trials, subcutaneous Burosumab increased serum phosphorus levels in pediatric and adult patients with XLH.With the development of phase 1-3 clinical trials of Burosumab in children and adults with XLH, the efficacy and safety of Burosumab is proven to be superior to that of phosphate and calcitriol used in traditional therapy.This review aims to investigate the physiopathology and treatment of HR and to enhance the recognition of HR. Key words: Rickets; Hypophosphatemia; Fibroblast growth factor 23; Osteomalacia; 1, 25(OH)2D

Analysis of clinical diagnosis and treatment of 20 children with hypophosphatemic rickets

Objective To analyze the clinical diagnosis and treatment data of 20 children with hypophosphatemic rickets (HR) in order to improve the clinical diagnosis and treatment of HR. Methods The retrospective analysis of clinical data of 20 cases with HR who were hospitalized at Children′s Hospital of Nanjing Medical University from May, 2010 to April, 2016 was performed to summarize the clinical characteristics.All patients were analyzed for the phosphate regulating gene with homologies to endopeptidase on the X chromosome(PHEX) gene by direct sequencing.If no mutations were detected, multiplex ligation-dependent probe amplification analysis was performed. Results All of the 20 cases with HR showed different degrees of growth retardation and typical X-ray rickets.After treatment, the clinical features were improved.Height standard deviation score (HSDS) was improved significantly with longer treatment time, and the difference was statistically significant(P=0.027). There was a correlation between the blood phosphorus fluctuation and secondary hyperparathyroidism(P<0.05). Nineteen cases had PHEX gene mutations.Truncating mutations was the most frequent mutation type, and 4 new mutations were found. Conclusions Clinical characte-ristics, laboratory test results and X-ray examination are important clinical index for the diagnosis of HR, and PHEX gene test can be used as an important auxiliary diagnostic tool.Early diagnosis and treatment can significantly improve the clinical manifestations of the patients. Key words: Hypophosphatemic rickets; Diagnosis; Treatment

Hypercalcemic Disorders in Children.

ABSTRACTHypercalcemia is defined as a serum calcium concentration that is greater than two standard deviations above the normal mean, which in children may vary with age and sex, reflecting changes in the normal physiology at each developmental stage. Hypercalcemic disorders in children may present with hypotonia, poor feeding, vomiting, constipation, abdominal pain, lethargy, polyuria, dehydration, failure to thrive, and seizures. In severe cases renal failure, pancreatitis and reduced consciousness may also occur and older children and adolescents may present with psychiatric symptoms. The causes of hypercalcemia in children can be classified as parathyroid hormone (PTH)‐dependent or PTH‐independent, and may be congenital or acquired. PTH‐independent hypercalcemia, ie, hypercalcemia associated with a suppressed PTH, is commoner in children than PTH‐dependent hypercalcemia. Acquired causes of PTH‐independent hypercalcemia in children include hypervitaminosis; granulomatous disorders, and endocrinopathies. Congenital syndromes associated with PTH‐independent hypercalcemia include idiopathic infantile hypercalcemia (IIH), William's syndrome, and inborn errors of metabolism. PTH‐dependent hypercalcemia is usually caused by parathyroid tumors, which may give rise to primary hyperparathyroidism (PHPT) or tertiary hyperparathyroidism, which usually arises in association with chronic renal failure and in the treatment of hypophosphatemic rickets. Acquired causes of PTH‐dependent hypercalcemia in neonates include maternal hypocalcemia and extracorporeal membrane oxygenation. PHPT usually occurs as an isolated nonsyndromic and nonhereditary endocrinopathy, but may also occur as a hereditary hypercalcemic disorder such as familial hypocalciuric hypercalcemia, neonatal severe primary hyperparathyroidism, and familial isolated primary hyperparathyroidism, and less commonly, as part of inherited complex syndromic disorders such as multiple endocrine neoplasia (MEN). Advances in identifying the genetic causes have resulted in increased understanding of the underlying biological pathways and improvements in diagnosis. The management of symptomatic hypercalcemia includes interventions such as fluids, antiresorptive medications, and parathyroid surgery. This article presents a clinical, biochemical, and genetic approach to investigating the causes of pediatric hypercalcemia. © 2017 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.

Treatment of hypophosphatemic rickets in generalized arterial calcification of infancy (GACI) without worsening of vascular calcification.

Patients with generalized arterial calcification of infancy (GACI) develop vascular calcifications early in life. About half of them die within the first 6 months despite optimal medical care. A subset of those who survive eventually develop hypophosphatemic rickets. Since hypophosphatemia and hyperphosphaturia have been previously associated with increased survival in GACI patients, physicians often avoid phosphate repletion as treatment for rickets. As a consequence, GACI patients develop severe rachitic complications such as short stature and skeletal deformities. It appears that the recognition of hypophosphatemia later in life in some GACI patients is a consequence of having survived the first few months of life, and not the cause of their survival per se. Here, we report the long-term follow-up of a GACI patient who was phosphate-repleted for his rickets for more than 7 years without worsening of vascular calcification.

Therapeutic management of hypophosphatemic rickets from infancy to adulthood

In children, hypophosphatemic rickets (HR) is revealed by delayed walking, waddling gait, leg bowing, enlarged cartilages, bone pain, craniostenosis, spontaneous dental abscesses, and growth failure. If undiagnosed during childhood, patients with hypophosphatemia present with bone and/or joint pain, fractures, mineralization defects such as osteomalacia, entesopathy, severe dental anomalies, hearing loss, and fatigue. Healing rickets is the initial endpoint of treatment in children. Therapy aims at counteracting consequences of FGF23 excess, i.e. oral phosphorus supplementation with multiple daily intakes to compensate for renal phosphate wasting and active vitamin D analogs (alfacalcidol or calcitriol) to counter the 1,25-diOH-vitamin D deficiency. Corrective surgeries for residual leg bowing at the end of growth are occasionally performed. In absence of consensus regarding indications of the treatment in adults, it is generally accepted that medical treatment should be reinitiated (or maintained) in symptomatic patients to reduce pain, which may be due to bone microfractures and/or osteomalacia. In addition to the conventional treatment, optimal care of symptomatic patients requires pharmacological and non-pharmacological management of pain and joint stiffness, through appropriated rehabilitation. Much attention should be given to the dental and periodontal manifestations of HR. Besides vitamin D analogs and phosphate supplements that improve tooth mineralization, rigorous oral hygiene, active endodontic treatment of root abscesses and preventive protection of teeth surfaces are recommended. Current outcomes of this therapy are still not optimal, and therapies targeting the pathophysiology of the disease, i.e. FGF23 excess, are desirable. In this review, medical, dental, surgical, and contributions of various expertises to the treatment of HR are described, with an effort to highlight the importance of coordinated care.

Treatment of Hypophosphatemic Rickets with Phosphate and Active Vitamin D in Japan: A Questionnaire-based Survey.

Hereditary hypophosphatemic rickets represented by X-linked hypophosphatemic rickets (XLH) is a rare disorder characterized by hypophosphatemia, elevated alkaline phosphatase (ALP) and undermineralization of bone. Active vitamin D and phosphate are administered to correct hypophosphatemia and elevation of ALP. Overtreatment with phosphate leads to secondary hyperparathyroidism, and a large dose of active vitamin D has a risk of hypercalciuria. To understand the situation concerning treatment of patients with hereditary hypophosphatemic rickets in Japan, we conducted a questionnaire survey of pediatric endocrinologists. Answers were obtained from 53 out of 68 hospitals where the pediatric endocrinologists worked. One hundred and thirty-five patients were treated in 28 hospitals during November 2009 and May 2010; 126 patients suffered from hereditary hypophosphatemic rickets, and 9 had hypophosphatemia caused by other miscellaneous reasons. The distribution of patient age was as follows: 27 (21%) were between 6 mo and 6 yr of age, 39 (31%) were between 6 and 12 yr of age, and 60 (48%) were more than 12 yr of age. Active vitamin D was given to 123 patients, and phosphate was given to 106 patients. As for the dose of phosphorus, 37.2-58.1 mg/kg/d was given divided into 2 to 6 aliquots. There were various control targets of treatment, including serum phosphate, serum ALP, rachitic change, urinary Ca/Cr, parathyroid hormone and growth. It is very important to avoid side effects of these treatments. No evidence is available about the optimal dose of phosphate or number of administrations in the treatment of patients with hypophosphatemic rickets. Although there is a recommendation for clinical management of patients with hypophosphatemic rickets, we should set a clinical guideline for it in Japan.

Treatment of Hypophosphatemic Rickets with Phosphate and Active Vitamin D in Japan: A Questionnaire-based Survey

Hereditary hypophosphatemic rickets represented by X-linked hypophosphatemic rickets (XLH) is a rare disorder characterized by hypophosphatemia, elevated alkaline phosphatase (ALP) and undermineralization of bone. Active vitamin D and phosphate are administered to correct hypophosphatemia and elevation of ALP. Overtreatment with phosphate leads to secondary hyperparathyroidism, and a large dose of active vitamin D has a risk of hypercalciuria. To understand the situation concerning treatment of patients with hereditary hypophosphatemic rickets in Japan, we conducted a questionnaire survey of pediatric endocrinologists. Answers were obtained from 53 out of 68 hospitals where the pediatric endocrinologists worked. One hundred and thirty-five patients were treated in 28 hospitals during November 2009 and May 2010; 126 patients suffered from hereditary hypophosphatemic rickets, and 9 had hypophosphatemia caused by other miscellaneous reasons. The distribution of patient age was as follows: 27 (21%) were between 6 mo and 6 yr of age, 39 (31%) were between 6 and 12 yr of age, and 60 (48%) were more than 12 yr of age. Active vitamin D was given to 123 patients, and phosphate was given to 106 patients. As for the dose of phosphorus, 37.2–58.1 mg/kg/d was given divided into 2 to 6 aliquots. There were various control targets of treatment, including serum phosphate, serum ALP, rachitic change, urinary Ca/Cr, parathyroid hormone and growth. It is very important to avoid side effects of these treatments. No evidence is available about the optimal dose of phosphate or number of administrations in the treatment of patients with hypophosphatemic rickets. Although there is a recommendation for clinical management of patients with hypophosphatemic rickets, we should set a clinical guideline for it in Japan.

Dental hypersensitivity due to hypophosphataemia?

Case ReportsDental hypersensitivity due to hypophosphataemia?H Hintze, A Wenzel and F KruhofferH HintzeSearch for more papers by this author, A WenzelSearch for more papers by this author and F KruhofferSearch for more papers by this authorPublished Online:28 Jan 2014https://doi.org/10.1259/dmfr.19.2.2079147SectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail About Previous article Next article FiguresReferencesRelatedDetailsCited byDental manifestations and treatment of hypophosphatemic rickets: A case report and review of literature30 January 2023 | BDJ Open, Vol. 9, No. 1 Volume 19, Issue 2May 1990Pages: 49-87 © 1990 The Authors. Published by the British Institute of Radiology History Published onlineJanuary 28,2014 Metrics Download PDF