Problem list Short stature - PowerPoint Presentation

Slide1

Problem list

Short stature

Genua

valgum

Early

tooth decay

loozer

zone fracture

Enthesopathy

Severe bone pain

R

ecurrent

fx

( fragility

fracture

)

Serum

phosphorus

: low

Serum calcium :

normal

Serum PTH :

normal

Serum ALP :

normal

Serum 25(OH)D : normal

Hyperphosphaturia

: +

Hypercalciuria

: -

Hypophosphatemic rickets (HR)

Hypophosphatemia is due to

elevated levels of FGF23

that result in

renal phosphate wasting.

J Pediatr Endocr Met 2015; 28(1-2): 211–216

Clinical

features :

Delay in

walking

in

the first years of life

S

hort stature

Growth

retardation

Bone deformity (

apparent after the age of 1

or 2 years)

Femoral

and tibia

bowing

, and

genua

vara

and

valga

Females

generally have

less

relevant

bone involvement

than

males.

Diseases

associated with

CPPD

under 40

yr

old

Disorder

Probability of association

Hemochromatosis

Definite

Hyperparathyroidism

Definite

Hypophosphatasia

Definite

Hypomagnesemia

Definite

Gitleman's syndrome

Definite Hypothyroidism

Probable

Gout

Possible

X-linked

hypophosphatemic

rickets

Possible

Familial hypocalciuric hypercalcemia

Possible

Hemosiderosis

Possible

CPPD

Radiographs

of the anterior-posterior views of right

knees ,

the right

shoulder and pelvis showing

linear calcifications in the areas of the medial and

lateral menisci

of the knee

,

in the

chondral

cartilage of the proximal

humerus

and

symphysis

pubis and both hip joints respectively consistent with chondrocalcinosis (arrow).

Treatment

The indications

for treatment of adult patients

are more

controversial

.

Affected adults are

considered candidates for pharmacologic therapy

:

pseudofractures

B

one pain,

presumably due to

osteomalacia

A

fter fractures or osteotomies

Therapy is not recommended in asymptomatic patients who do not have pseudofractures. 2015

Treatment

Once the decision is made to initiate therapy, it

is best

to start at a low dose of

calcitriol

and phosphate (

to avoid diarrhea from phosphate) and gradually

increase therapy

over several months

.

Some clinicians maintain

a

“high

dose” phase

for

up

to 1 year:

maximum calcitriol dose 25 ng/kg/dayPhosphate dose : 20 to 40 mg/kg four divided doses (up to a maximum of 2 g/day) .

Serum calcium, phosphorus, and creatinine levels, urine calcium and creatinine, are routinely monitored on a monthly basis during dose escalation.

Treatment

After 1

year on high-dose therapy, patients are

switched

to

a long-term

“maintenance” phase

with

10 -

20

ng/kg/day

of

calcitriol

and

no change in the dose of phosphate.

While patients are on maintenance therapy, we monitor serum and urine biochemistries at least every 3 to 4 months.

Treatment

A

24-hour

urine

phosphorus

measurement

is often useful to gauge compliance with therapy

.

Serum

PTH

concentration should be

measured

at

yearly intervals

as appropriate

.

Complications

Diarrhea

and

gastrointestinal

Nephrocalcinosis

Tertiary hyperparathyroidism

Complications

Factors that could influence the progression to tertiary hyperparathyroidism are an

early age of treatment onset, longer duration of treatment, high doses of elementary phosphorus (100 mg/kg/day) and very high PTH plasma levels (around 400

pg

/mL) .

Participants

:

Twenty-eight adults with XLH participated in a 4-month dose-escalation study (

0.05–0.6

mg/kg); 22 entered a 12-month extension study (0.1–1 mg/kg

).

Intervention:

KRN23 was injected

sc

every 28 days

.

Main Outcome Measure:

The main outcome measure was the proportion of subjects

attaining normal

serum Pi and safety

.

Results: During dose escalation, TmP/GFR

, Pi, and 1,25(OH)2D increased, peaking at 7 days for TmP/GFR and Pi and at 3–7 days for 1,25(OH)2D, remaining above (TmP/GFR, Pi) or near [1,25(OH)2D] pre-dose levels at trough. After each of the four escalating doses, peak Pi was between 2.5 and 4.5 mg/dL.Conclusions:

Monthly KRN23 significantly increased serum Pi, TmP/GFR, and 1,25(OH)2D in all subjects.KRN23 has potential for effectively treating XLH.

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