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Mechanisms for abnormal mineral metabolism in chronic kidney disease
Figuras y tablas -
Figure 1

Mechanisms for abnormal mineral metabolism in chronic kidney disease

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 1 All‐cause mortality.
Figuras y tablas -
Analysis 1.1

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 1 All‐cause mortality.

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 2 Fracture.
Figuras y tablas -
Analysis 1.2

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 2 Fracture.

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 3 Development of bone pain.
Figuras y tablas -
Analysis 1.3

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 3 Development of bone pain.

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 4 Parathyroidectomy.
Figuras y tablas -
Analysis 1.4

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 4 Parathyroidectomy.

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 5 Development of subperiosteal erosions.
Figuras y tablas -
Analysis 1.5

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 5 Development of subperiosteal erosions.

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 6 Resolution of subperiosteal erosions.
Figuras y tablas -
Analysis 1.6

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 6 Resolution of subperiosteal erosions.

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 7 Development of vascular calcification.
Figuras y tablas -
Analysis 1.7

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 7 Development of vascular calcification.

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 8 Progression of vascular calcification.
Figuras y tablas -
Analysis 1.8

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 8 Progression of vascular calcification.

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 9 Development of osteitis fibrosa.
Figuras y tablas -
Analysis 1.9

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 9 Development of osteitis fibrosa.

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 10 Development of osteomalacia.
Figuras y tablas -
Analysis 1.10

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 10 Development of osteomalacia.

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 11 End of treatment parathyroid hormone (pg/mL).
Figuras y tablas -
Analysis 1.11

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 11 End of treatment parathyroid hormone (pg/mL).

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 12 Reduction in parathyroid hormone level by 30%.
Figuras y tablas -
Analysis 1.12

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 12 Reduction in parathyroid hormone level by 30%.

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 13 End of treatment serum phosphorus (mg/dL).
Figuras y tablas -
Analysis 1.13

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 13 End of treatment serum phosphorus (mg/dL).

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 14 One or more episodes of hyperphosphataemia.
Figuras y tablas -
Analysis 1.14

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 14 One or more episodes of hyperphosphataemia.

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 15 End of treatment serum calcium (mg/dL).
Figuras y tablas -
Analysis 1.15

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 15 End of treatment serum calcium (mg/dL).

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 16 One or more episodes of hypercalcaemia.
Figuras y tablas -
Analysis 1.16

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 16 One or more episodes of hypercalcaemia.

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 17 Withdrawal of treatment due to hypercalcaemia.
Figuras y tablas -
Analysis 1.17

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 17 Withdrawal of treatment due to hypercalcaemia.

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 18 One or more episodes of elevated calcium x phosphorus product.
Figuras y tablas -
Analysis 1.18

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 18 One or more episodes of elevated calcium x phosphorus product.

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 19 End of treatment alkaline phosphatase (U/L).
Figuras y tablas -
Analysis 1.19

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 19 End of treatment alkaline phosphatase (U/L).

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Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 1 All‐cause mortality.
Figuras y tablas -
Analysis 2.1

Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 1 All‐cause mortality.

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Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 2 Fracture.
Figuras y tablas -
Analysis 2.2

Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 2 Fracture.

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Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 3 Improvement in bone pain.
Figuras y tablas -
Analysis 2.3

Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 3 Improvement in bone pain.

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Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 4 Improvement in bone histomorphometry.
Figuras y tablas -
Analysis 2.4

Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 4 Improvement in bone histomorphometry.

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Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 5 End of treatment parathyroid hormone (pg/mL).
Figuras y tablas -
Analysis 2.5

Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 5 End of treatment parathyroid hormone (pg/mL).

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Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 6 End of treatment serum phosphorus (mg/dL).
Figuras y tablas -
Analysis 2.6

Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 6 End of treatment serum phosphorus (mg/dL).

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Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 7 One or more episodes of hyperphosphataemia.
Figuras y tablas -
Analysis 2.7

Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 7 One or more episodes of hyperphosphataemia.

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Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 8 End of treatment serum calcium (mg/dL).
Figuras y tablas -
Analysis 2.8

Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 8 End of treatment serum calcium (mg/dL).

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Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 10 One or more episodes of hypercalcaemia.
Figuras y tablas -
Analysis 2.10

Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 10 One or more episodes of hypercalcaemia.

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Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 11 Withdrawal of treatment due to hypercalcaemia.
Figuras y tablas -
Analysis 2.11

Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 11 Withdrawal of treatment due to hypercalcaemia.

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Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 12 Reduction in parathyroid hormone concentration by 50%.
Figuras y tablas -
Analysis 2.12

Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 12 Reduction in parathyroid hormone concentration by 50%.

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Comparison 3 IV versus oral vitamin D compounds, Outcome 1 All‐cause mortality.
Figuras y tablas -
Analysis 3.1

Comparison 3 IV versus oral vitamin D compounds, Outcome 1 All‐cause mortality.

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Comparison 3 IV versus oral vitamin D compounds, Outcome 2 Fracture.
Figuras y tablas -
Analysis 3.2

Comparison 3 IV versus oral vitamin D compounds, Outcome 2 Fracture.

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Comparison 3 IV versus oral vitamin D compounds, Outcome 3 End of treatment absolute BMD femoral neck (g/cm²).
Figuras y tablas -
Analysis 3.3

Comparison 3 IV versus oral vitamin D compounds, Outcome 3 End of treatment absolute BMD femoral neck (g/cm²).

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Comparison 3 IV versus oral vitamin D compounds, Outcome 4 End of treatment absolute BMD lumbar spine (g/cm²).
Figuras y tablas -
Analysis 3.4

Comparison 3 IV versus oral vitamin D compounds, Outcome 4 End of treatment absolute BMD lumbar spine (g/cm²).

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Comparison 3 IV versus oral vitamin D compounds, Outcome 5 End of treatment parathyroid hormone (pg/mL).
Figuras y tablas -
Analysis 3.5

Comparison 3 IV versus oral vitamin D compounds, Outcome 5 End of treatment parathyroid hormone (pg/mL).

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Comparison 3 IV versus oral vitamin D compounds, Outcome 6 End of treatment serum phosphorus (mg/dL).
Figuras y tablas -
Analysis 3.6

Comparison 3 IV versus oral vitamin D compounds, Outcome 6 End of treatment serum phosphorus (mg/dL).

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Comparison 3 IV versus oral vitamin D compounds, Outcome 7 One or more episodes of hyperphosphataemia.
Figuras y tablas -
Analysis 3.7

Comparison 3 IV versus oral vitamin D compounds, Outcome 7 One or more episodes of hyperphosphataemia.

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Comparison 3 IV versus oral vitamin D compounds, Outcome 8 End of treatment serum calcium (mg/dL).
Figuras y tablas -
Analysis 3.8

Comparison 3 IV versus oral vitamin D compounds, Outcome 8 End of treatment serum calcium (mg/dL).

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Comparison 3 IV versus oral vitamin D compounds, Outcome 9 One of more episodes of hypercalcaemia.
Figuras y tablas -
Analysis 3.9

Comparison 3 IV versus oral vitamin D compounds, Outcome 9 One of more episodes of hypercalcaemia.

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Comparison 3 IV versus oral vitamin D compounds, Outcome 10 End of treatment alkaline phosphatase (U/L).
Figuras y tablas -
Analysis 3.10

Comparison 3 IV versus oral vitamin D compounds, Outcome 10 End of treatment alkaline phosphatase (U/L).

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Comparison 4 Intraperitoneal (IP) versus oral vitamin D compounds, Outcome 1 Improvement in bone histomorphometry.
Figuras y tablas -
Analysis 4.1

Comparison 4 Intraperitoneal (IP) versus oral vitamin D compounds, Outcome 1 Improvement in bone histomorphometry.

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Comparison 4 Intraperitoneal (IP) versus oral vitamin D compounds, Outcome 2 End of treatment parathyroid hormone (pg/mL).
Figuras y tablas -
Analysis 4.2

Comparison 4 Intraperitoneal (IP) versus oral vitamin D compounds, Outcome 2 End of treatment parathyroid hormone (pg/mL).

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Comparison 4 Intraperitoneal (IP) versus oral vitamin D compounds, Outcome 3 One or more episodes of hyperphosphataemia.
Figuras y tablas -
Analysis 4.3

Comparison 4 Intraperitoneal (IP) versus oral vitamin D compounds, Outcome 3 One or more episodes of hyperphosphataemia.

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Comparison 4 Intraperitoneal (IP) versus oral vitamin D compounds, Outcome 4 One or more episodes of hypercalcaemia.
Figuras y tablas -
Analysis 4.4

Comparison 4 Intraperitoneal (IP) versus oral vitamin D compounds, Outcome 4 One or more episodes of hypercalcaemia.

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Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 1 Fracture.
Figuras y tablas -
Analysis 5.1

Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 1 Fracture.

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Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 2 End of treatment parathyroid hormone (pg/mL).
Figuras y tablas -
Analysis 5.2

Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 2 End of treatment parathyroid hormone (pg/mL).

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Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 3 One or more episodes of hyperphosphataemia.
Figuras y tablas -
Analysis 5.3

Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 3 One or more episodes of hyperphosphataemia.

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Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 4 End of treatment serum phosphorus (mg/dL).
Figuras y tablas -
Analysis 5.4

Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 4 End of treatment serum phosphorus (mg/dL).

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Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 5 One of more episodes of hypercalcaemia.
Figuras y tablas -
Analysis 5.5

Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 5 One of more episodes of hypercalcaemia.

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Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 6 End of treatment serum calcium (mg/dL).
Figuras y tablas -
Analysis 5.6

Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 6 End of treatment serum calcium (mg/dL).

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Table 1. Stages of chronic kidney disease (KDOQI)

CKD stage

GFR range

1

≥ 90 mL/min/1.73 m² with kidney damage for ≥3 months as defined by structural or functional abnormalities of the kidney

2

60‐89 mL/min/1.73 m²

3

30‐59 mL/min

4

15‐29 mL/min

5

< 15 mL/min or dialysis
Figuras y tablas -
Table 1. Stages of chronic kidney disease (KDOQI)
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Table 2. Summary of extractable data for meta‐analysis

Comparison

(studies)

Studies

Patients

Studies with efficacy data extractable for meta‐analysis

Studies with adverse event data available

Studies/meta‐analysis (range)

Vitamin D versus placebo (18)

All studies combined

18

1297

14

8

1‐7

Established vitamin D

10

850

7

5

1‐4

Newer vitamin D

8

447

7

3

1‐6

Vitamin D versus vitamin D compound (13)

Active vitamin D versus vitamin D3

2

53

1

2

1‐2

Calcitriol versus another established vitamin D

3

101

1

2

1‐2

Established versus newer vitamin D

5

414

2

3

1‐2

Other comparisons

3

59

Meta‐analysis not possible

Vitamin D versus calcium (1)

All studies combined

1

47

Meta‐analysis not possible

IV versus oral vitamin D (12)

All studies combined

12

720

8

8

1‐6

Intraperitoneal versus oral vitamin D (3)

All studies combined

3

74

Meta‐analysis not possible

Subcutaneous versus oral vitamin D (1)

All studies combined

1

6

Meta‐analysis not possible

Intermittent versus daily vitamin D (5)

All studies combined

5

140

1

4

1‐4

Differing dosing schedules (7)

Differing frequency

3

57

Meta‐analysis not possible

Differing doses

3

195

Meta‐analysis not possible

Morning versus evening dosing

1

13

Meta‐analysis not possible
Figuras y tablas -
Table 2. Summary of extractable data for meta‐analysis
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Table 3. Current guidelines for the use of vitamin D compounds in chronic kidney disease

Guideline

Country

Year

Recommendation

Kidney Disease Outcomes Quality Initiative

USA

2003

Patients treated with HD or PD with serum levels of intact PTH levels > 300 pg/mL) (33.0 pmol/L) should receive an active vitamin D sterol (such as calcitriol, alfacalcidol, paricalcitol, or doxercalciferol) to reduce the serum levels of PTH to a target range of 150‐300 pg/mL (16.5‐33.0 pmol/L). (EVIDENCE)

The intermittent, IV administration of calcitriol is more effective than daily oral calcitriol in lowering serum PTH levels. (EVIDENCE)

In patients with corrected serum calcium and/or phosphorus levels above the target range, a study of alternative vitamin D analogs, such as paricalcitol or doxercalciferol may be warranted. (OPINION)

When either HD or PD patients are treated with active vitamin D sterols, management should integrate the changes in serum calcium, serum phosphorus, and plasma PTH.

Caring for Australasians with Renal Impairment

Australasia

2006

Oral calcitriol (intermittent or pulsed) is effective at lowering parathyroid hormone levels in patients on PD (Level II evidence).

Vitamin D and its analogs, either given orally daily, orally intermittently, or intravenously are effective at lowering PTH levels in patients on HD (Level I/II evidence).

Oral calcitriol is effective for the prevention or treatment of hyperparathyroidism in most patients on HD or PD. IV calcitriol may be more effective at lowering PTH levels and be less likely to cause hypercalcaemia but the lack of well‐designed studies of sufficient size prevents a more definitive statement.

Vitamin D analogs are effective at lowering PTH but clinical studies proving their effectiveness with fewer side‐effects prevents are either lacking or not definitive. On the basis of current evidence there is little reason to recommend their use over oral or IV calcitriol.

British Renal Society

UK

2007

The relative importance of hyperparathyroidism as a risk factor for premature vascular disease is difficult to determine from observational studies and no informative RCTs exist.

There is no doubt that a serum PTH concentration over 4 times the normal limit is associated with increased risk of significant bone disease and should therefore be avoided by medical (or if necessary surgical) management of hyperparathyroidism.

In the absence of firm evidence, individual clinicians should decide on the degree to which hyperparathyroidism should be corrects and how this should be achieved.

European Best Practice Guidelines (EBPG)

Europe

2002

No guideline

Europe ‐‐ expert panel (including members from Fresenius Medical Care) (not EBPG)

Europe

2001

PTH above 9‐18 pmol/L (78‐156 pg/mL) may well be treated with small daily doses of active vitamin D. IV pulse administration does not have any advantage over oral route. No evidence from direct comparative studies to show any superiority of maxacalcitol, doxercalciferol, or paricalcitol over calcitriol or alfacalcidol.

Canadian Society of Nephrology

Canada

2006

Avoid intact PTH (iPTH) levels < 100 pg/mL (10.6 pmol/L (Grade C); iPTH levels > 500 pg/mL (53 pmol/L) should be treated if accompanied by symptoms or clinical signs of hyperparathyroidism. Vitamin D analogs should be used in conjunction with a specialist.

There is insufficient evidence to recommend use of novel vitamin D analogs (grade D, opinion)

HD ‐ haemodialysis; PD ‐ peritoneal dialysis
Figuras y tablas -
Table 3. Current guidelines for the use of vitamin D compounds in chronic kidney disease
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Comparison 1. Vitamin D compounds versus placebo/no treatment

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

5

233

Risk Ratio (M‐H, Random, 95% CI)

1.34 [0.34, 5.24]

1.1 Established vitamin D compounds

3

168

Risk Ratio (M‐H, Random, 95% CI)

1.11 [0.24, 5.05]

1.2 Newer vitamin D compounds

2

65

Risk Ratio (M‐H, Random, 95% CI)

3.00 [0.13, 68.26]

2 Fracture Show forest plot

4

181

Risk Ratio (M‐H, Random, 95% CI)

1.0 [0.06, 15.41]

2.1 Established vitamin D compounds

3

103

Risk Ratio (M‐H, Random, 95% CI)

1.0 [0.06, 15.41]

2.2 Newer vitamin D compounds

1

78

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3 Development of bone pain Show forest plot

4

109

Risk Ratio (M‐H, Random, 95% CI)

0.29 [0.03, 2.63]

3.1 Established vitamin D compounds

3

74

Risk Ratio (M‐H, Random, 95% CI)

0.41 [0.02, 9.25]

3.2 Newer vitamin D compounds

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.20 [0.01, 4.65]

4 Parathyroidectomy Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

4.1 Established vitamin D compounds

2

133

Risk Ratio (M‐H, Random, 95% CI)

0.82 [0.05, 12.47]

4.2 Newer vitamin D compounds

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5 Development of subperiosteal erosions Show forest plot

3

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

5.1 Established vitamin D compounds

3

120

Risk Ratio (M‐H, Random, 95% CI)

0.41 [0.07, 2.38]

5.2 Newer vitamin D compounds

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

6 Resolution of subperiosteal erosions Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

6.1 Established vitamin D compounds

1

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

6.2 Newer vitamin D compounds

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7 Development of vascular calcification Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

7.1 Established vitamin D compounds

2

103

Risk Ratio (M‐H, Random, 95% CI)

1.09 [0.45, 2.67]

7.2 Newer vitamin D compounds

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8 Progression of vascular calcification Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

8.1 Established vitamin D compounds

1

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8.2 Newer vitamin D compounds

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9 Development of osteitis fibrosa Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

9.1 Established vitamin D compounds

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

9.2 Newer vitamin D compounds

0

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

10 Development of osteomalacia Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

10.1 Established vitamin D compounds

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

10.2 Newer vitamin D compounds

0

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

11 End of treatment parathyroid hormone (pg/mL) Show forest plot

6

212

Mean Difference (IV, Random, 95% CI)

‐196.05 [‐298.43, ‐93.66]

11.1 Established vitamin D compounds

4

104

Mean Difference (IV, Random, 95% CI)

‐220.54 [‐473.63, 32.55]

11.2 Newer vitamin D compounds

2

108

Mean Difference (IV, Random, 95% CI)

‐183.88 [‐217.88, ‐149.89]

12 Reduction in parathyroid hormone level by 30% Show forest plot

7

361

Risk Ratio (M‐H, Random, 95% CI)

5.90 [3.17, 10.96]

12.1 Established vitamin D compounds

1

47

Risk Ratio (M‐H, Random, 95% CI)

2.72 [1.12, 6.61]

12.2 Newer vitamin D compounds

6

314

Risk Ratio (M‐H, Random, 95% CI)

7.05 [3.82, 13.04]

13 End of treatment serum phosphorus (mg/dL) Show forest plot

2

105

Mean Difference (IV, Random, 95% CI)

0.70 [0.08, 1.33]

13.1 Established vitamin D compounds

1

27

Mean Difference (IV, Random, 95% CI)

0.60 [‐0.40, 1.60]

13.2 Newer vitamin D compounds

1

78

Mean Difference (IV, Random, 95% CI)

0.77 [‐0.04, 1.58]

14 One or more episodes of hyperphosphataemia Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

14.1 Established vitamin D compound

2

59

Risk Ratio (M‐H, Random, 95% CI)

1.57 [0.97, 2.54]

14.2 Newer vitamin D compound

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

15 End of treatment serum calcium (mg/dL) Show forest plot

2

105

Mean Difference (IV, Random, 95% CI)

0.36 [‐0.26, 0.98]

15.1 Established vitamin D compounds

1

27

Mean Difference (IV, Random, 95% CI)

0.0 [‐0.61, 0.61]

15.2 Newer vitamin D compounds

1

78

Mean Difference (IV, Random, 95% CI)

0.64 [0.22, 1.06]

16 One or more episodes of hypercalcaemia Show forest plot

5

182

Risk Ratio (M‐H, Random, 95% CI)

3.80 [0.90, 16.12]

16.1 Established vitamin D compounds

3

74

Risk Ratio (M‐H, Random, 95% CI)

1.96 [0.62, 6.22]

16.2 Newer vitamin D compounds

2

108

Risk Ratio (M‐H, Random, 95% CI)

11.97 [1.48, 96.58]

17 Withdrawal of treatment due to hypercalcaemia Show forest plot

4

196

Risk Ratio (M‐H, Random, 95% CI)

4.17 [1.36, 12.77]

17.1 Established vitamin D compounds

2

88

Risk Ratio (M‐H, Random, 95% CI)

3.66 [0.96, 14.03]

17.2 Newer vitamin D compounds

2

108

Risk Ratio (M‐H, Random, 95% CI)

5.61 [0.74, 42.45]

18 One or more episodes of elevated calcium x phosphorus product Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

18.1 Established vitamin D compounds

1

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

18.2 Newer vitamin D compounds

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

19 End of treatment alkaline phosphatase (U/L) Show forest plot

3

135

Mean Difference (IV, Random, 95% CI)

‐24.34 [‐44.34, ‐4.33]

19.1 Established vitamin D compounds

1

27

Mean Difference (IV, Random, 95% CI)

‐16.0 [‐54.83, 22.83]

19.2 Newer vitamin D compounds

2

108

Mean Difference (IV, Random, 95% CI)

‐27.35 [‐50.69, ‐4.01]
Figuras y tablas -
Comparison 1. Vitamin D compounds versus placebo/no treatment
Ir a la tabla de la revisión
Comparison 2. Vitamin D compound versus vitamin D compound

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

1.1 New versus established vitamin D compounds

2

103

Risk Ratio (M‐H, Random, 95% CI)

2.0 [0.19, 21.21]

2 Fracture Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

2.1 New versus established vitamin D compounds

1

73

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3 Improvement in bone pain Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

3.1 Active vitamin D compound versus vitamin D3

1

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

4 Improvement in bone histomorphometry Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

4.1 Active vitamin D compound versus vitamin D3

1

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5 End of treatment parathyroid hormone (pg/mL) Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Totals not selected

5.1 Active vitamin D compound versus vitamin D3

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

5.2 Calcitriol versus other established vitamin D compounds

1

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

5.3 New versus established vitamin D compounds

1

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

6 End of treatment serum phosphorus (mg/dL) Show forest plot

3

Mean Difference (IV, Random, 95% CI)

Subtotals only

6.1 Active vitamin D compound versus vitamin D3

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

6.2 Calcitriol versus another established vitamin D

2

91

Mean Difference (IV, Random, 95% CI)

0.52 [‐0.40, 1.44]

6.3 New versus established vitamin D compounds

1

73

Mean Difference (IV, Random, 95% CI)

‐0.31 [‐1.05, 0.43]

7 One or more episodes of hyperphosphataemia Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

7.1 Active vitamin D compound versus vitamin D3

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7.2 Calcitriol versus other established vitamin D compounds

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7.3 New versus established vitamin D compounds

1

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8 End of treatment serum calcium (mg/dL) Show forest plot

4

Mean Difference (IV, Random, 95% CI)

Subtotals only

8.1 Active vitamin D compound versus vitamin D3

1

31

Mean Difference (IV, Random, 95% CI)

0.85 [0.35, 1.35]

8.2 Calcitriol versus other established vitamin D compounds

2

91

Mean Difference (IV, Random, 95% CI)

1.00 [‐0.56, 2.57]

8.3 New versus established vitamin D compounds

1

73

Mean Difference (IV, Random, 95% CI)

0.30 [‐0.11, 0.71]

9 End of treatment alkaline phosphatase (U/L)

0

Mean Difference (IV, Random, 95% CI)

Totals not selected

9.1 Active vitamin D versus vitamin D3

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

9.2 Calcitriol versus other established vitamin D compounds

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

9.3 New versus established vitamin D compounds

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

10 One or more episodes of hypercalcaemia Show forest plot

5

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

10.1 Active vitamin D compound versus vitamin D3

2

53

Risk Ratio (M‐H, Random, 95% CI)

9.56 [1.32, 69.04]

10.2 Calcitriol versus other established vitamin D compounds

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10.3 New versus established vitamin D compounds

3

125

Risk Ratio (M‐H, Random, 95% CI)

0.82 [0.26, 2.54]

11 Withdrawal of treatment due to hypercalcaemia Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

11.1 Active vitamin D compound versus vitamin D3

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

11.2 Calcitriol versus other established vitamin D compounds

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

11.3 New versus established vitamin D compounds

2

52

Risk Ratio (M‐H, Random, 95% CI)

0.61 [0.17, 2.22]

12 Reduction in parathyroid hormone concentration by 50% Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

12.1 New versus established vitamin D compounds

1

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Figuras y tablas -
Comparison 2. Vitamin D compound versus vitamin D compound
Ir a la tabla de la revisión
Comparison 3. IV versus oral vitamin D compounds

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

2 Fracture Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

3 End of treatment absolute BMD femoral neck (g/cm²) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

4 End of treatment absolute BMD lumbar spine (g/cm²) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

5 End of treatment parathyroid hormone (pg/mL) Show forest plot

8

171

Mean Difference (IV, Random, 95% CI)

‐76.20 [‐150.92, ‐1.48]

6 End of treatment serum phosphorus (mg/dL) Show forest plot

5

112

Mean Difference (IV, Random, 95% CI)

‐0.30 [‐0.58, ‐0.03]

7 One or more episodes of hyperphosphataemia Show forest plot

5

102

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.65, 1.48]

8 End of treatment serum calcium (mg/dL) Show forest plot

6

146

Mean Difference (IV, Random, 95% CI)

0.08 [‐0.35, 0.52]

9 One of more episodes of hypercalcaemia Show forest plot

6

128

Risk Ratio (M‐H, Random, 95% CI)

1.11 [0.80, 1.52]

10 End of treatment alkaline phosphatase (U/L) Show forest plot

4

116

Mean Difference (IV, Random, 95% CI)

3.61 [‐50.06, 57.28]
Figuras y tablas -
Comparison 3. IV versus oral vitamin D compounds
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Comparison 4. Intraperitoneal (IP) versus oral vitamin D compounds

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Improvement in bone histomorphometry Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

2 End of treatment parathyroid hormone (pg/mL) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

3 One or more episodes of hyperphosphataemia Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

4 One or more episodes of hypercalcaemia Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected
Figuras y tablas -
Comparison 4. Intraperitoneal (IP) versus oral vitamin D compounds
Ir a la tabla de la revisión
Comparison 5. Intermittent versus daily vitamin D compounds

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Fracture Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

2 End of treatment parathyroid hormone (pg/mL) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

3 One or more episodes of hyperphosphataemia Show forest plot

3

97

Risk Ratio (M‐H, Random, 95% CI)

1.74 [0.44, 6.79]

4 End of treatment serum phosphorus (mg/dL) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

5 One of more episodes of hypercalcaemia Show forest plot

4

118

Risk Ratio (M‐H, Random, 95% CI)

1.15 [0.36, 3.69]

6 End of treatment serum calcium (mg/dL) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

7 End of treatment alkaline phosphatase (U/L)

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]
Figuras y tablas -
Comparison 5. Intermittent versus daily vitamin D compounds
Ir a la tabla de la revisión