JUSINDO, Vol. 6 No. 2, Juli 2024

p-ISSN: 2303-288X, e-ISSN: 2541-7207

Jurnal Sehat Indonesia: Vol. 6, No. 2, Juli 2024 | 681

Vitamin D Supplementation Dose as The Prevention of Fragility Fracture

In Chronic Kidney Disease Patient: A Systematic Review

Aldico J Sapardan

, Rashida S Djatnika

RSUD Kabupaten Bekasi, Indonesia

Email: rashidasabahat12@gmail.com

ABSTRACT

Keywords:

CKD affects more than 10% of the global population. It can

cause osteoporosis and increase the risk of fractures,

especially as CKD becomes more serious. In CKD, mineral

and bone disorders (CKD-MBD) cause abnormalities in how

the body processes vitamin D, calcium, phosphorus, or

parathyroid hormone (PTH). It can also affect bone strength

and cause calcium build-up in the soft tissues. Treatment

usually starts with correcting the chemical abnormalities that

occur in the body due to CKD-MBD before focusing on

osteoporosis and fractures. A study review spanning 2010 to

2023 investigated optimal vitamin D supplementation doses in

CKD patients, indicating varied outcomes influenced by

factors like dosage, duration, and population characteristics.

Doses ranged from 800 to 8,000 IU/day of cholecalciferol,

with recommendations contingent on serum 25(OH)D levels.

Vitamin D; Supplementation;

Prevention; Fragility fracture;

Chronic kidney disease

Coresponden Author: Rashida S Djatnika

Email: [email protected]

Artikel dengan akses terbuka dibawah lisensi

Introduction

Chronic kidney disease (CKD) is a degenerative disorder that affects more than 10% of

the general population worldwide, or over 800 million people (Kovesdy, 2022). Patients with

chronic renal illness are more prone to osteoporosis and fractures than the general population.

The increase in fractures in people in general and those with CKD is due to bone mass loss

associated with ageing (Pimentel et al., 2021). The metabolic imbalances found in CKD affect

both the restructuring and mineralization processes. These imbalances are now acknowledged

to manifest in the initial stages of renal disease, even when kidney function appears normal.

This occurs prior to the onset of biochemical signs indicating CKD mineral and bone disorder

(CKD-MBD), which typically emerges as the kidney's condition decreases. This condition

affects the majority of CKD patients in stages 4 and 5 (Evenepoel et al., 2021; Khairallah &

Nickolas, 2018).

CKD-MBD is a condition marked by abnormalities in the metabolism of vitamin D,

calcium, phosphorus, and parathyroid hormone (PTH It also results in problems with bone

strength, bone growth, and bone mineralisation, as well as calcium build-up in soft tissues such

as blood vessels (Tinawi, 2022). Lack of active vitamin D, phosphate build-up, decreased

calcium absorption from the gut, as well as insufficient production of a substance called alpha

Jurnal Sehat Indonesia: Vol. 6, No. 2, Juli 2024 | 682

klotho by the kidneys, and increased levels of fibroblast growth factor 23 (FGF23) all

contribute. All these factors together lead to secondary hyperparathyroidism and structural

changes in the bones, resulting in decreased bone mineral density and increased risk of fractures

(Jean et al., 2017; Kužma et al., 2021).

In CKD, the levels of circulating 25(OH)D start declining from the initial stages due to

various factors. These include skin hyperpigmentation, decreased synthesis of cholecalciferol

in the skin, dietary limitations, impaired absorption in the intestines, heightened catabolism of

vitamin D, and significant urinary excretion of vitamin D-binding protein (DBP) and vitamin

D metabolites, particularly in cases of severe proteinuria (Ketteler et al., 2017). When there's a

deficiency in vitamin D, the reduction in calcium absorption is offset by a rise in PTH. This

hormone promotes the conversion of 25(OH)D into 1,25(OH)2D (Ureña Torres et al., 2022).

Treatment for people with chronic kidney disease (CKD) should start by addressing the

chemical abnormalities in the body associated with bone and mineral problems, before trying

specific treatments for osteoporosis or fractures. The 2017 KDIGO guidelines recommend the

first step to address the mineral and metabolic imbalances that occur within the body due to

CKD. One of the main problems associated with CKD is secondary hyperparathyroidism,

which means that the parathyroid glands in the body become overactive. This often occurs early

in CKD and gets worse over time as the kidneys become less functional. The guidelines also

suggest treatment for mineral balance issues such as phosphate and calcium, as well as vitamin

D deficiency in stage 3-5 CKD patients who have persistently high or above-normal parathyroid

hormone (PTH) levels.(Ketteler et al., 2017). We also provided the results of a study that looked

at whether supplementing with vitamin D could help improve the outcome of such treatment.

Research Methods

Trial Design

Our study was conducted as an international cohort study, incorporating expertise-based

control measures along with randomized controlled trial methodologies. Further details

regarding eligibility criteria, interventions, outcomes, and statistical analyses were provided.

Search Strategy

To investigate the optimal dosage of vitamin D supplementation for preventing osteoporosis in

CKD patients, we conducted a comprehensive review. This review encompassed the KDIGO

2017 clinical practice guideline update, PubMed, and Springer publications spanning from 2010

to 2023. Additionally, we scrutinized the reference lists of identified articles to uncover further

relevant studies. Our search terms included "bone fragility fractures in chronic kidney disease

patients," "management of osteoporosis in CKD patients," "Vitamin D supplementation for

mineral and bone disease in CKD patients," "Vitamin D and renal disease," and "vitamin D as

treatment of secondary hyperparathyroidism."

Following the PICOS (participants, interventions, comparisons, outcomes, and study design)

principle, we focused on (P) patients with CKD, particularly those exhibiting signs of secondary

hyperparathyroidism; (I) the dosage of vitamin D supplementation; (C/O) the outcome of serum

PTH levels; and (S) randomized controlled trials (RCTs) and cohort studies.

Inclusion And Exclusion Criteria

The eligible article should have the following inclusion criteria (1) RCTs about the

management of osteoporosis or mineral and bone disease in CKD patients (2) CKD patients

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given Vitamin D supplementation statistical outcomes on PTH level;(3) RCTs years published

from 2010 until 2023. Studies were excluded if any of the following characteristics, (1) RCTS

published before years of 2010; (2) no interest outcomes reported.

Results and Discussion

The studies resumed on the following table:

Table 1 The studies resumed

Study

Population

Intervention

Result

Moe SM, Saifullah A,

LaClair RE et al; (2010)

This was a study

conducted over 3

months, using a

randomised and

double-blind method,

in stage 3 and 4 CKD

patients who were

vitamin D deficient

and had problems

with parathyroid

hormone (PTH).

cholecalciferol

(4000 IU/d × 1

month

In the cholecalciferol

group, parathyroid

hormone (PTH)

decreased by 10% ±

31% (P = 0.16).

Marckmann P,

Agerskov H et al;

(2012)

We conducted a

parallel double-blind

intervention study in

CKD patients

undergoing

haemodialysis (HD)

and CKD patients not

undergoing

haemodialysis.

40,000 IU of

cholecalciferol

orally per week

for 8 weeks

In patients not

undergoing

haemodialysis, a

significant increase

in 1,25-diOHD (n =

13, P < 0.01) and a

decrease in

parathyroid hormone

(PTH) (n = 13, P <

0.001) could be

observed.

Cupisti A, Egidi MF,

Vigo V et al; (2015)

There were 405 pre-

existing patients with

chronic kidney

disease (CKD) stages

2-4.

10,000 IU once-a-

week for 12

months

25-hydroxyvitamin

D levels increase and

parathyroid hormone

(PTH) levels

decrease.

Sprague SM, Crawford

PW, Melnick JZ et al.

(2016)

There were 429

subjects balanced

between the studies,

with stage 3 or 4

CKD, secondary

hyperparathyroidism,

and vitamin D

deficiency.

calcifediol (30 or

60 µg) equal to

1200 IU or 2400

IU/ day

for 26 weeks

The reduction of

iPTH by ≥30%

increased gradually

with treatment

duration, reaching

22%, 40%, and 50%

at 12, 26, and 52

weeks, respectively.

Yadav AK, Vivek K et

al; (2018)

There were 120

subjects with stable

stage G3-G4 chronic

kidney disease

(CKD), non-diabetics,

both male and female,

with ages ranging

between 18 and 70

years.

oral dose of

300.000 IU of

cholecalciferol for

16 weeks

Intact parathyroid

hormone (iPTH)

levels decreased in

the group receiving

cholecalciferol.

Jurnal Sehat Indonesia: Vol. 6, No. 2, Juli 2024 | 684

Westerberg A, Sterner

G, Ljunggren O et al;

(2018)

There were 95

patients with stage 3-

4 CKD.

cholecalciferol

8000 IU/day for

12 weeks

Calcidiol levels

increased to 162 ±

49 mmol/L in

patients receiving

cholecalciferol,

while parathyroid

hormone (PTH)

levels remained

stable.

Omrani HR, Daraizade

A; 2018

There were 80

patients undergoing

haemodialysis with

ages ranging from 30

to 85 years.

cholecalciferol

(50000 units, 3

times a week) and

calcitriol (0.25

μg, once a day)

for 3 months

There was no

significant difference

between the two

treatment groups.

Both groups reduced

iPTH levels and thus

improved secondary

hyperparathyroidism.

Conclusion

Our review showed that the dose of vitamin D affecting PTH concentrations which leads

to treating CKD-MBD remains inconsistent between studies. This is due to various durations,

dose, and population characteristics. The range dose of vitamin D(cholecalciferol) starts from

800 IU up to 8.000 IU/day. As a result, the suggested dose is based on the annual assessment's

serum 25(OH)D level.

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