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ACQUIRED VITAMIN D RESISTANT RICKETS
IN PATIENTS WITH HUMAN
IMMUNODEFFICEINCY VIRUS DUE TO
TENOFOVIR ANTIRETROVIRAL TREATMENT
Sonia Iyobosa Omoregie, Olivia Ohikhuare
Scientific Leader: Olesia Singh
KYIV MEDICAL UNIVERSITY
Introduction
 Rickets is known as reduced bone mass with calcification
disorders causing large amounts of unmineralized bone tissue
before closure of the epiphysis in adolescence.
 Rickets can either be caused by Vitamin D deficiency or
mineralization defects.
 Vitamin D deficiency can be caused by deficiency in vitamin D
reuptake or absorption, defective 25-hyroxylation, loss of
vitamin binding protein, defective 1--25 hydroxylation, (Kim
2017).
Case report
 Our case of study is Patient A, 12 years old female brought into the hospital with severe X-
deformation of the legs called Genu Valgum.
 The X-deformation developed during last 6 months
 Patient A, born with Human Immunodeficiency virus (HIV), was on a different antiretroviral
drug prior and was previously absent of any complications, and later changed to Tenofovir
which she has been on for the past two and a half years.
Patient A on Tenofovir treatment Patient A before Tenofovir treatment
Lab Result of Patient A
Biochemical Test Urine Analysis
Densitometry of patient A.
A Z-score of below -2 indicates low bone density
Z-score L1-L4 = - 3.5 SD
Z-score left femur =-4.1 SD
Z-score right femur = - 4.4 SD
AIM OF STUDY:
To find if there is a connection between Tenofovir and development
of vitamin D, calcium and phosphate disorders leading to severe
osteomalacia.
MATERIALS AND METHODS OF STUDY:
◦ Analysis was done with scientific research papers between 2009 and 2019 for
literature connecting osteomalacia (vitamin D resistant rickets) to use of
Tenofovir.
◦ Our key words were Vitamin D, Vitamin D deficiency, Osteomalacia, calcium,
phosphate, Antiretroviral therapy/drugs, Tenofovir, HIV.
◦ Using our key words we narrowed our search down to 19 scientific research
papers.
◦ These include various studies done about effects of Tenofovir on all age groups.
Ashley D. Holec, Subhra Mandal, Pavan Kumar Prathipati, Christopher J. Destache, Nucleotide Reverse
Transcriptase Inhibitors: A Thorough Review, Present Status and Future Perspective as HIV Therapeutics,
Current HIV Research, Volume 13, Issue 6, 2017
Evidence of Osteopathies in Research
 In research done by T. Brown in 2006, 884 HIV patients were surveyed. 67% had reduced BMD
as well as 15% of those patients having osteoporosis.
 There have been 81 various research papers written about the status of vitamin D in
patients with HIV and 49% of them include information about decrease in bone health. 23%
note the use of Tenofovir increased risk of developing proximal renal tubulopathy ( as
manifested with patient A) perhaps ultimately causing development of osteomalacia.
95% 5%
Normal Patient without fanconi syndrome
Fanconi syndrome
75%
25%
In patients with
Fanconi syndrome
Normal Fanconi manifesation
hypophosphatemia, decrease in spine and
total body z score
Pediatric study showing Fanconi Developed in
Pediatric Patient taking Tenofovir
What is Fanconi Syndrome?
 Fanconi Syndrome is also known as Proximal Renal Tubulopathy. It may be congenital or
acquired. Congenitally, it develops at birth. Some acquired causes: chemotherapy,
antiretroviral treatment or vitamin D deficiency.
 Main symptoms are proteinuria, glucosuria, acidic pH, deformation of legs ( knocked knee or
bow legs),and hypophosphatemia, syndrome of osteomalacia.
Yuka Kinoshita, Seiji Fukumoto, X-Linked Hypophosphatemia and FGF23-Related Hypophosphatemic Diseases: Prospect for New Treatment, Endocrine Reviews, Volume 39, Issue 3, June 2018,
Mechanism of development of osteomalacia in patients who take
Tenofovir
Conclusion
 In children who take Tenofovir, 5% may develop Fanconi’s
Syndrome.
 Before Tenofovir treatment, 25-hydroxy vitamin D, calcium and
phosphate in blood and urine analysis should be checked.
 The child must reach optimal vitamin D level before beginning
treatment and then take vitamin D 2000 IU/daily.
 Every 3 months biochemical (calcium, phosphate, and alkaline
phosphatase) and urinalysis should be checked.
 In cases of Fanconi’s syndrome development, vitamin D
(4000IU/Daily or calcitriol) should be taken with treatment.
Acquired Vitamin D resistant Rickets

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Acquired Vitamin D resistant Rickets

  • 1. ACQUIRED VITAMIN D RESISTANT RICKETS IN PATIENTS WITH HUMAN IMMUNODEFFICEINCY VIRUS DUE TO TENOFOVIR ANTIRETROVIRAL TREATMENT Sonia Iyobosa Omoregie, Olivia Ohikhuare Scientific Leader: Olesia Singh KYIV MEDICAL UNIVERSITY
  • 2. Introduction  Rickets is known as reduced bone mass with calcification disorders causing large amounts of unmineralized bone tissue before closure of the epiphysis in adolescence.  Rickets can either be caused by Vitamin D deficiency or mineralization defects.  Vitamin D deficiency can be caused by deficiency in vitamin D reuptake or absorption, defective 25-hyroxylation, loss of vitamin binding protein, defective 1--25 hydroxylation, (Kim 2017).
  • 3. Case report  Our case of study is Patient A, 12 years old female brought into the hospital with severe X- deformation of the legs called Genu Valgum.  The X-deformation developed during last 6 months  Patient A, born with Human Immunodeficiency virus (HIV), was on a different antiretroviral drug prior and was previously absent of any complications, and later changed to Tenofovir which she has been on for the past two and a half years. Patient A on Tenofovir treatment Patient A before Tenofovir treatment
  • 4. Lab Result of Patient A Biochemical Test Urine Analysis
  • 5. Densitometry of patient A. A Z-score of below -2 indicates low bone density Z-score L1-L4 = - 3.5 SD Z-score left femur =-4.1 SD Z-score right femur = - 4.4 SD
  • 6. AIM OF STUDY: To find if there is a connection between Tenofovir and development of vitamin D, calcium and phosphate disorders leading to severe osteomalacia. MATERIALS AND METHODS OF STUDY: ◦ Analysis was done with scientific research papers between 2009 and 2019 for literature connecting osteomalacia (vitamin D resistant rickets) to use of Tenofovir. ◦ Our key words were Vitamin D, Vitamin D deficiency, Osteomalacia, calcium, phosphate, Antiretroviral therapy/drugs, Tenofovir, HIV. ◦ Using our key words we narrowed our search down to 19 scientific research papers. ◦ These include various studies done about effects of Tenofovir on all age groups.
  • 7. Ashley D. Holec, Subhra Mandal, Pavan Kumar Prathipati, Christopher J. Destache, Nucleotide Reverse Transcriptase Inhibitors: A Thorough Review, Present Status and Future Perspective as HIV Therapeutics, Current HIV Research, Volume 13, Issue 6, 2017
  • 8. Evidence of Osteopathies in Research  In research done by T. Brown in 2006, 884 HIV patients were surveyed. 67% had reduced BMD as well as 15% of those patients having osteoporosis.  There have been 81 various research papers written about the status of vitamin D in patients with HIV and 49% of them include information about decrease in bone health. 23% note the use of Tenofovir increased risk of developing proximal renal tubulopathy ( as manifested with patient A) perhaps ultimately causing development of osteomalacia. 95% 5% Normal Patient without fanconi syndrome Fanconi syndrome 75% 25% In patients with Fanconi syndrome Normal Fanconi manifesation hypophosphatemia, decrease in spine and total body z score Pediatric study showing Fanconi Developed in Pediatric Patient taking Tenofovir
  • 9. What is Fanconi Syndrome?  Fanconi Syndrome is also known as Proximal Renal Tubulopathy. It may be congenital or acquired. Congenitally, it develops at birth. Some acquired causes: chemotherapy, antiretroviral treatment or vitamin D deficiency.  Main symptoms are proteinuria, glucosuria, acidic pH, deformation of legs ( knocked knee or bow legs),and hypophosphatemia, syndrome of osteomalacia. Yuka Kinoshita, Seiji Fukumoto, X-Linked Hypophosphatemia and FGF23-Related Hypophosphatemic Diseases: Prospect for New Treatment, Endocrine Reviews, Volume 39, Issue 3, June 2018, Mechanism of development of osteomalacia in patients who take Tenofovir
  • 10. Conclusion  In children who take Tenofovir, 5% may develop Fanconi’s Syndrome.  Before Tenofovir treatment, 25-hydroxy vitamin D, calcium and phosphate in blood and urine analysis should be checked.  The child must reach optimal vitamin D level before beginning treatment and then take vitamin D 2000 IU/daily.  Every 3 months biochemical (calcium, phosphate, and alkaline phosphatase) and urinalysis should be checked.  In cases of Fanconi’s syndrome development, vitamin D (4000IU/Daily or calcitriol) should be taken with treatment.

Editor's Notes

  1. In this review, we analyse the relationship between HIV patients on antiretroviral drug: Tenofovir and acquired vitamin D resistant tickets
  2. According to the anamnesis, lab analysis, methodological data including risk factors of Tenofivor and understanding the mechanism of actions. It is necessary to make differential diagnosis of the following: Congenital vitamin D resistant rickets, Vitamin D deficiency rickets and Fanconi syndrome.
  3. Influence of Tenofovir on Vitamin D People with HIV have been shown to have 3 times greater risk of osteoporosis than people without HIV. This is partially due to the virus impairing bone strength because glycoproteins of HIV-1 impair utilization of calcium and reduce ability of osteoblasts. The risk of osteopathy is also increased with the use of antiretroviral drugs. Disturbances of vitamin D metabolism also occur due to increased production of cytochrome P450 (CYP3A4) which is triggered by induction of different enzymes and even Tenofovir can induce production of CYP3A4. This increases degradation of vitamin D. (Gröber 2012)
  4. 4000IU/Daily)There was a high level of phosphate waste and severe osteomalacia, high dosage of vitamin D should be administered in order to reduce risk of drug induced osteopathy. These results give further support for the role of vitamin D (4000IU/daily) as a modulator of human antiviral and antibacterial responses, and suggest inclusion when taking Tenofovir.
  5. the red area shows osteoid (large arrow) and the green area is mineralized bone (small arrow)