Bone and Mineral Disorders in Chronic Kidney Disease Parker Gregg Internal Medicine R3

Bone and Mineral Disorders in Chronic Kidney Disease

Parker GreggInternal Medicine R3

Learning Objectives

List 3 different medications for the treatment of hyperparathyroidism in CKD and how they differ

Differentiate secondary hyperparathyroidism, adynamic bone disease, and other bone/mineral disorders by lab values and clinical presentation

Describe the mechanisms by which bone and mineral disorders develop in CKD

Table of Contents

Monitoring and treatment of bone and mineral disorders in CKD

MKSAP cases to illustrate types of bone and mineral disorders in CKD

How things go so wrong in CKD

Review of normal calcium, phos, PTH, and vitamin D homeostasis

NORMAL CALCIUM, PHOS, PTH, AND VITAMIN D HOMEOSTASIS

Key Points

PTH does everything it can to increase ECF calcium, but to keep phos relatively balanced it wastes phos in the

urine

ECF calcium and vitamin D decrease PTH secretion; phos increases PTH secretion

Vitamin D’s main goal is to increase bone mineralization

ECF calcium comes from guts, bones, and kidneys

Calcium and Phosphate

Homeostasis

Key Points


urine




Vitamin D Metabolism

Cholecalciferol (D3)

25-hydroxycholecalciferol

1,25-dihydroxycholecalciferol

Increased intestinal absorption of calcium

Liver

Kidney

Gut

Activation PTH

Inhibition

Vitamin D Effects on Calcium and PO4

Key Points


urine




PTH Effects on Calcium and PO4

Calcium and PO4

via increased

production of

vitamin D Calcium and PO4

PO4

Calcium

Key Points


urine




Ca Vit D

Parathyroid gland

Parathyroid Hormone Regulation

High calcium and 1,25-OH vit D decrease PTH

secretion

High phos stimulates PTH

PO4

Key Points


urine




WHEN THINGS START TO GO WRONG

CKD Bone and mineral

disorders

Initiation of CKD-BMD

Decreased GFR

Decreased filtration of phos

Hyperphosphatemia

Hypocalcemia

Increased PTH

Early secondary hyperparathyroidism

maintains normal calcium and phos levels


Calcium and PO4

Calcium

PO4

Calcium and PO4

via increased

production of

vitamin D

Secondary Hyperparathyroidism

Osteitis fibrosa cystica (High Turnover Bone Disease)

Radiographic sclerosis, cystic bone

lesions, and subperiosteal bone

resorption

Elevated PTH and AlkPhos from high

bone turnover

Osteitis fibrosa cystica (High Turnover Bone Disease)

Brown tumor in the distal ulna

Elevated PTH and AlkPhos from high

bone turnover

Tertiary Hyperparathyroidism

Parathyroid hyperplasia that no longer responds to

calcium

Autonomous secretion of PTH

Hyperplastic gland doesn’t involute

Secondary Hyperparathyroidism (High Turnover Bone

Disease)

Adynamic Bone Disease

(Low Turnover Bone Disease)

Undersuppression of PTH Oversuppression of PTH

PTH Effects on Calcium and PO4

Calcium and PO4

via increased

production of

vitamin D Calcium and PO4

PO4

Calcium

Adynamic Bone Disease (Low Turnover Bone Disease)

Bone Pain Fractures

Vascular Calcification

Hypercalcemia

Low Bone Turnover

Extraosseous Calcification

Vascular Calcification

Increased Mortality

18%

CKD 3-5

19%

Hemodialysis

50%

Peritoneal Dialysis

Adynamic Bone DiseaseNo Adynamic Bone Disease



Caused by oversuppression of PTH

Therefore…

PTH is

Bone specific AlkPhos is

LOW*

LOW/NORMAL

*PTH <100. Can see in patients with PTH 100-450, but is harder to diagnose.

Disorder Phos Calcium PTH AlkPhos

Secondary Hyperpara-thyroidism

Adynamic Bone Disease

*Adynamic bone disease not excluded in PTH 100-450

Lab Values in CKD-BMD

−/ −/ * −/

Osteomalacia

Vitamin D deficiency

Profound hypocalcemia

Aluminum exposure

Mixed Osteodystrophy

OsteomalaciaHigh or low

turnover bone disease

B2-Microglobulin Amyloidosis(Dialysis-Related Amyloidosis)

B2-Microglobulin Amyloidosis

(Dialysis-Related

Amyloidosis)

MKSAP QUESTIONS

MKSAP Question 1

A 59 year-old woman is evaluated for a 2-week history of right hip pain. She has chronic kidney disease treated with peritoneal dialysis. Medications are epoetin alfa, calcium acetate, calcitriol, and a multivitamin. She has no history of exposure to aluminum-containing medications.

On physical examination, vital signs are normal. There is tenderness over the right lateral trochanter. Internal and external rotation of the hip elicit pain.

Laboratory studies:Phosphorus 5.6 mg/dLCalcium 10.2 mg/dLAlkaline phosphatase 86 U/LIntact PTH 21 pg/mL1,25-dihydroxyvitamin D 52 pg/mL25-hydroxyvitamin D 15 ng/mL

MKSAP Question 1

Plain radiograph of the right hip shows diffuse osteopenia. An area of lucency is seen along the medial aspect of the femoral neck on the right side consistent with a stress fracture.

MKSAP Question 1

Which of the following is most likely the cause of this patient’s bone disease?A. Adynamic bone diseaseB. B2-Microglobulin-associated amyloidosisC. Osteitis fibrosa cysticaD. Osteomalacia

MKSAP Question 1

Osteopenia, fracture, bone pain, serum PTH level <100 pg/mL, and normal AlkPhos level are consistent with adynamic bone disease, which is a leading cause of bone disorders in patients with stage 5 CKD.

Risk factors: advanced age, DM, poor nutrition, and oversuppression of PTH with therapeutic agents

MKSAP Question 1

This patient’s 1,25-dihydroxyvitamin D level >30 pg/mL is consistent with repletion of vitamin D stores with calcitriol. The relatively low 25-hydroxyvitamin D level may be caused by reduced cutaneous synthesis and decreased dietary intake. Decreased hepatic 25-hydroxylation also may occur in patients with CKD.

MKSAP Question 1

Osteitis fibrosa cystica: hyperphosphatemia, hypocalcemia, and 1,25-vitD deficiency -> stimulate PTH secretion -> increase bone turnover. Radiographic sclerosis and subperiosteal bone resorption, elevated PTH, elevated AlkPhos

MKSAP Question 1

B2-microglobulin-associated amyloidosis: cystic bone lesion at the end of long bones that can enlarge over time, resulting in pathologic fractures

Osteomalacia: uncommon. Usually after exposure to aluminum-containing phosphate binders. Usually have elevated serum PTH.

MKSAP Question 1

Adynamic bone disease is a major cause of bone disease in patients with stage 5 CKD and usually manifests as osteopenia, fractures, and bone pain accompanied by a serum PTH level

below 100 pg/mL and a normal alkaline phosphatase level.

Take Home Point

A 33 year-old woman comes for follow up examination for a left fibula fracture due to a fall 1 week ago. She has hypertension and stage 5 CKD treated with home hemodialysis. Medications are lisinopril, sevelamer, epoetin alfa, paricalcitol, and kidney vitamins.

MKSAP Question 2

On physical examination, temperature is normal, blood pressure is 130/70 mmHg, pulse rate is 88/min, and respiration rate is 12/min. BMI is 29. Cardiopulmonary exam is normal. An arteriovenous fistula is present in the left forearm. Except for a cast on her left leg, musculoskeletal examination is normal and reveals no bone pain.

MKSAP Question 2

Laboratory studies:Hemoglobin 10.3 g/dLAlbumin 3.5 g/dLPhosphorus 5.8 mg/dLCalcium 8.4 mg/dLParathyroid hormone 700 pg/mLAlkaline phosphatase 330 U/L

MKSAP Question 2

Which of the following is the most likely cause of this patient’s bone disease?A. Adynamic bone diseaseB. Avascular necrosisC. OsteoporosisD. Secondary hyperparathyroidism

MKSAP Question 2

CKD is associated with progressive alterations in mineral and bone metabolism that can cause bone disease. In patients with ESRD, the kidney’s inability to excrete phosphorus leads to hyperphosphatemia. Loss of kidney function also is associated with 1,25-vitD deficiency. Hyperphosphatemia along with decreased 1,25-vitD levels result in hypocalcemia, which leads to direct stimulation of PTH secretion.

MKSAP Question 2

Furthermore, decreased 1,25-vitD levels cause increased production of PTH. Therefore, bone disease due to secondary hyperparathyroidism, the most common bone pathologic finding seen in patients with ESRD, develops. This patient’s hyperphosphatemia, hypocalcemia, and elevated serum PTH and AlkPhos are consistent with secondary hyperparathyroidism.

MKSAP Question 2


Adynamic bone disease: hypoparathyroidism caused by excess vitamin D intake and/or calcium loading

Osteoporosis: low bone mass, associated with reduced bone strength and increased risk of fractures. Does not affect the concentrations of serum calcium, phosphorus, or AlkPhos

MKSAP Question 2

Avascular necrosis: transient or permanent lack of blood supply to bone, causing death of bone and bone marrow infarction that results in mechanical failure. Typically present with chronic bone pain and not fracture.

MKSAP Question 2

Bone disease due to secondary hyperparathyroidism commonly occurs

in patients with ESRD and may be associated with elevated serum PTH

and alkaline phosphatase levels, hyperphosphatemia, and

hypocalcemia.

Take Home Point

MONITORING & TREATMENT

Monitoring (KDOQI Guidelines)

Serum Ca and Phos PTH Vitamin D Alkaline

Phosphatase

Stage 3 Q 6-12 months

At least annually

Yearly, replete as

needed--


Q 6-12 months

Yearly, replete as

neededYearly


Q 3-6 months

Yearly, replete as

neededYearly

FIRST INTERVENTION?

54 y/o M with stage 3 CKDCa PO4 PTH

Initial Presentation 8.2 5.8 43

Phosphate Restriction

WHAT’S NEXT?

Ca PO4 PTHInitial Presentation 8.2 5.8 43

6 Months Later 7.8 5.7 50

54 y/o M with stage 3 CKD

Phos Binders

Calcium Phos Binders:- Calcium Carbonate

(Tums)- Calcium Acetate

(Phoslo)

Non-Calcium Phos Binders:- Sevelamer (Renagel,

Renvela)- Lanthanum (PhosRenal)- Less used:

- Aluminum Hydroxide- Magnesium

Hydroxide- Niacin


Initial Presentation 8.2 5.8 436 Months Later 7.8 5.7 106

WHAT’S ELSE DO YOU CHECK?

Vitamin D Analogs

Nutritional deficiency

Cholecalciferol or ergocalciferol


Initial Presentation 8.2 5.8 436 Months Later 7.8 5.7 106

1 Year Later 7.0 6.5 648

WHAT’S NEXT?

Vitamin D Analogs

Nutritional deficiency

If PTH still elevated with phos binder and vit D supplementation…

Switch to active vitamin D derivatives:- Calcitriol (1,25-dihydroxyvitamin D)- Paracalcitol (Zemplar) with dialysis

Cholecalciferol or ergocalciferol

54 y/o M with stage 4 CKD

WHAT’S NEXT?

Ca PO4 PTHInitial Presentation 8.2 5.8 43

6 Months Later 7.8 5.7 1061 Year Later 7.0 6.5 6481 Year Later 7.5 5.0 700

Calcimimetic Therapy

Cinacalcet (Sensipar)

Does not act on the GI tract to increase absorption of calcium

Parathyroidectomy

Treatment of Adynamic Bone Disease

STAHP!!

Allow PTH secretion to rise

Decrease serum calcium

Stop vitamin D analogs

Switch to non-calcium phos binders

Learning Objectives

List 3 different medications for the treatment of hyperparathyroidism in CKD and how they differ

Differentiate secondary hyperparathyroidism, adynamic bone disease, and other bone/mineral disorders by lab values and clinical presentation

Describe the mechanisms by which bone and mineral disorders develop in CKD

Take Home Points

Secondary hyperparathyroidism is the end result of the natural progression of the abnormalities set in motion

by hyperphosphatemia

Phos binders, vitamin D analogs, and calcium analogs are all used to treat hyperparathyroidism

Adynamic Bone disease is common, and it is caused by oversuppression of PTH

You (yes, you!) can reason through how CKD-BMD happens

QUESTIONS?

Documents

Bone and Mineral Disorders in Chronic Kidney Disease Parker Gregg Internal Medicine R3