Osteoporosis Associated with Pregnancy and Lactation

O

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i

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A

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L

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o

n

Christopher

Kovacs,

MD,

FRCPC,

FACP,

FACE

University

Research

Professor

Professor

of

Medicine

(Endocrinology),

Obstetrics

&

Gynecology,

and

BioMedical

Sciences

Faculty

of

Medicine

-

Endocrinology

Memorial

University

of

Newfoundland

D

i

s

c

l

o

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u

r

e

■

No

relevant

conflicts

of

interest

■

This

area

is

both

a

clinical

interest

and

a

research

focus

for

me

C

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n

t

a

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i

o

n

-

1

■

Age

35

with

ankylosing

spondylitis,

treated

with

a

TNF

 blocker

■

Uneventful

first

pregnancy

and

began

 breastfeeding

■

Lactation

consultant

advised

that

baby’s

slow

weight

gain

meant

inadequate

milk

production

■

Instructed

her

to

pump

in

between

feeds

and

store

(not

use)

the

milk

(!)

■

Pumped

and

stored

as

much

milk

as

her

baby

received

directly

through

nursing

■

Two

months

into

breastfeeding,

felt

increasing

back

pain

■

Rheumatologist

adjusted

her

meds

but

no

relief

from

pain

■

Bent

over

to

move

her

baby

in

the

car

seat:

felt

and

heard

a

loud

crack

in

her

back

■

Presented

to

orthopedics

and

referred

to

endocrinology

in

 Calgary

Disclosed

when

I

saw

her

several

years

later

C

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a

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-

2

■

Spine

radiographs

 showed

compression

fractures

 of

30%

at

T11

and

40%

at

T12,

accompanied

by

 endplate

depressions

at

L2,

L3

and

L4

■

(These

radiographs

were

done

several

years

later

at

my

 institution)

C

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-

3

■

Vegetarian

with

high

phytate

 intake

■

Habitual

calcium

intake

of

750

mg

daily;

250

mg

supplement

during

pregnancy

to

reach

1,000

mg

daily

(vs.

1,200

mg

optimal

intake)

■

Habitual

vitamin

D

intake

3,800

IU

daily

through

 supplements

■

Ulnar

fracture

at

age

12

when

she

was

pushed

down

on

the

schoolyard

■

Ankle

fracture

at

age

17

when

she

fell 

downstairs

■

Twice

she

had

 3-

week

courses

of

prednisone

for

asthma

(15

mg

starting

 dose)

■

Attention

deficit

hyperactivity

disorder,

postpartum

depression,

iron

deficiency,

mild

psoriasis,

periodic

 vertigo

■

Sister

has

low

bone

mass

(“osteopenia”)

but

no

fractures

Determined

when

I

saw

her

several

years

later

C

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a

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i

o

n

-

4

■

Workup

for

secondary

causes

of

bone

loss

was

otherwise

 unremarkable

■

Whole

genome

sequencing

found

no

mutations

in

any

genes

related

to

osteoporosis,

bone

mass,

or

bone

metabolism

■

At

6

months

postpartum,

while

still

breastfeeding,

Lunar

DXA

revealed

 severe

bone

loss

at

the

lumbar

 spine:

■

Lumbar

spine

0.645

g/cm

2

or

Z-score

-

3.6

■

Total

hip

0.736

g/cm

2

or

Z-score

-

1.6

■

Femoral

neck

0.542

g/cm

2

or

Z-score

-

2.6

■

At

8

months

postpartum,

HR-

pQCT

showed

very

low

trabecular

bone

volumes

in

the

left

radius

and

tibia

P

r

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g

n

a

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c

y

M

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i

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g

p

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a

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c

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■

Average

human

fetus

at

term

has:

■

30

g

of

calcium

■

20

g

of

phosphorus

■

0.8

g

of

magnesium

■

80%

is

accreted

during

the

third

 trimester

■

The

rate

of

accretion

averages

150

mg

calcium

per

kg

fetal

weight

daily

■

60

mg

per

day

at

week

24

■

300-

350

mg

per

day

between the

35th

and

40th 

weeks

Kovacs

CS.

Physiol

Rev

2016;

96:449-

547

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i

t

■

Recommended

calcium

intake

 (non-

pregnant

or

pregnant)

is

1,200

mg

per

day

†

■

In

reproductive

age

North

American

women:

■

50

th

percentile

of

calcium

intake

is

~800-1,000

mg

daily

(varying

by

age

and

ethnicity)*

■

~25%

of

dietary

calcium

is

absorbed

■

Net

absorption

is

200-250

mg

of

calcium

■

This

is

insufficient

to

meet

the

fetal

demands

in

the

third

trimester,

and

well

below

the

combined

requirements

of

mother

and

 fetus

■

Assuming

25%

absorption,

would

require

an

extra

1,400

mg

daily

to

provide

the

350

mg

the

fetus

needs

during

the

late

third

trimester

Kovacs

CS.

Physiol

Rev

2016;

96:449-

547

†

Institute

of

Medicine,

Dietary

Reference

Intakes

for

Calcium

and

Vitamin

D,

2011

*NHANES

and

Health

Canada

data

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y

■

80%

of

calcium

is

actively

transported

to

the

fetus

in

third

 trimester

■

Doubling

of

intestinal 

calcium

absorption

begins

in

1st

 trimester

■

Calcium

balance

studies

predict

 maternal

skeletal

mineral

content

must

be

 increased

during

the

first

half

of

 pregnancy

■

Concurrent

2

to

 5-

fold

increase

in

calcitriol

(active

vitamin

D)

Kovacs

CS.

Physiol

Rev

2016;

96:449-

547

Urine

Serum

Ca

++

Calcium

Intake

Kovacs

CS

and

Kronenberg

HM.

Endocr

Rev

1997;

18:832-

872

P

r

e

g

n

a

n

c

y

■

Serum

calcium

falls

due

to

 albumin

■

Ionized

calcium

normal

■

PTH

low

*

■

Calcitriol

increases

2

to

5-

fold

■

PTHrP

increases

 steadily

■

Estradiol

increases

up

to

100x

■

Calcitonin

increased

■

Intestinal

calcium

absorption

doubled

*exception:

women

from

Asia

and

Africa

with

very

low

calcium

or

high

phytate

intakes

PTHrP

=

PTH-

related

protein

M

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a

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k

i

d

n

e

y

s

–

n

o

t

p

l

a

c

e

n

t

a

–

a

r

e

t

h

e

s

o

u

r

c

e

o

f

c

a

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c

i

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i

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d

u

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i

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g

p

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e

g

n

a

n

c

y

i

n

r

o

d

e

n

t

s

a

n

d

w

o

m

e

n

■

Anephric

women

have

low,

unchanging

calcitriol

 before

and

during

pregnancy

1

■

In

mice,

maternal

absence

of

Cyp27b1

(the

enzyme

that

creates

calcitriol)

obliterates

the

rise

in

 calcitriol

2

1

Turner

M.

Miner

Electrolyte

Metab

1988;

14:246-

252

2

Gillies

B.

J

Bone

Miner

Res

2018;

33:16-

26

C

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g

p

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n

a

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c

y

w

i

t

h

o

u

t

P

T

H

■

Inferred

that

calcitriol

rises

during

pregnancy

in

hypoparathyroid

women

in

whom

supplemental

calcitriol

needs

are

reduced

or

eliminated

■

Confirmed

in

aparathyroid

rodents,

including

mice

lacking

the

gene

encoding

PTH

Sweeney

L.

Endocr

Pract

.

2010;

16:459-

462

Kovacs

CS.

Physiol

Rev

2016;

96:449-

547

Kirby

BJ.

J

Bone

Mineral

Res

2013;

28:1987-

2000

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s

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p

t

i

o

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c

r

e

a

s

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s

d

u

r

i

n

g

p

r

e

g

n

a

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c

y

i

n

r

o

d

e

n

t

s

w

i

t

h

o

u

t

c

a

l

c

i

t

r

i

o

l

,

V

D

R

,

o

r

v

i

t

a

m

i

n

D

Kovacs

CS.

Physiol

Rev

2016;

96:449-

547

Ryan

BA.

J

Bone

Miner

Res

2022;

36:

2483-

2497

K

e

y

p

o

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t

s

a

b

o

u

t

p

r

e

g

n

a

n

c

y

■

The

fetal

demand

for

mineral

is

met

by

increased

intestinal

absorption

■

But

if

net

calcium

intake

is

low,

the

maternal

skeleton

must

be

resorbed

■

The

increase

in

calcium

absorption

is

driven

in

part

by

an

increase

in

calcitriol,

but

it’s

also

driven

by

unknown

factors

independent

of

 calcitriol

■

More

than

one

mechanism

kicks

in

to

ensure

calcium

delivery

■

Consequently,

calcium

delivery

is

maintained

despite

severe

vitamin

D

deficiency

C

a

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s

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s

k

e

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t

a

l

f

r

a

g

i

l

i

t

y

a

s

s

o

c

i

a

t

e

d

w

i

t

h

p

r

e

g

n

a

n

c

y

Nutritional

■

Low

dietary

calcium

intake

■

Dairy

avoidance

■

Lactose

intolerance

■

Low

vitamin

D

intake/vitamin

D

deficiency

■

High

phytate

intake

■

Anorexia

nervosa

Gastrointestinal

■

Celiac

disease

■

Crohn’s

disease

■

Cystic

fibrosis

■

Short

bowel

from

resections

■

Other

malabsorptive

disorders

Hormonal

■

Excess

PTHrP

from

placenta

or

breasts*

■

Primary

hyperparathyroidism

■

Hyperthyroidism

■

Cushing’s

syndrome

■

Chronic

oligoamenorrhea

■

Hypothalamic

amenorrhea

■

Pituitary

disorders

leading

to

sex

steroid

deficiency

■

Premature

ovarian

failure

Kovacs

CS

and

Ralston

SH.

Osteoporos

Int

2015;

26:2223-

2241

*each

source

has

also

been

found

to

cause

hypercalcemia

in

pregnancy

C

a

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s

o

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s

k

e

l

e

t

a

l

f

r

a

g

i

l

i

t

y

a

s

s

o

c

i

a

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e

d

w

i

t

h

p

r

e

g

n

a

n

c

y

Mechanical

■

Petite

frame

■

Low

body

weight

■

Low

peak

bone

mass

■

Excess

exercise

■

Increased

weight-

bearing

of

pregnancy

■

Lordotic

posture

of

pregnancy

■

Bedrest

■

Incomplete

recovery

from

prior

lactation?

Renal

■

Hypercalciuria/renal

calcium

leak

■

Chronic

renal

insufficiency

■

Renal

tubular

acidosis

Pharmacological

■

GnRH

analog

treatment

■

Progestin-

only

contraceptives

■

Glucocorticoids

■

Proton

pump

inhibitors

■

Heparin

■

Certain

anti-

seizure

medications

(phenytoin,

carbamazepine)

■

Cancer

chemotherapy

■

Alcohol

Kovacs

CS

and

Ralston

SH.

Osteoporos

Int

2015;

26:2223-

2241

C

a

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s

k

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a

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f

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a

g

i

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y

a

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w

i

t

h

p

r

e

g

n

a

n

c

y

Primary

disorders

of

bone

quality*

■

Osteogenesis

imperfecta

(COL1A1/1A2

mutations)

–

milder

forms

■

Osteopetrosis

and

other

sclerosing

bone

disorders

■

LRP5

inactivating

mutations

■

Wnt1

mutations

Connective

tissue

disorders

■

Ehlers-

Danlos

syndrome

■

Marfan

syndrome

*not

known

prior

to

pregnancy

Rheumatological

disorders

■

Rheumatoid

arthritis

■

Systemic

lupus

erythematosis

Other

non-

specified

genetic

disorders

■

Family

history

of

osteoporosis

or

skeletal

fragility

■

Positive

genetic

screen

for

other

bone

disorders

Idiopathic

osteoporosis

Being

a

primipara

Kovacs

CS

and

Ralston

SH.

Osteoporos

Int

2015;

26:2223-

2241

O

s

t

e

o

p

o

r

o

s

i

s

p

r

e

s

e

n

t

i

n

g

d

u

r

i

n

g

p

r

e

g

n

a

n

c

y

■

Occasionally

vertebral

crush

fractures

occur

during

late

pregnancy

■

Exact

frequency

 unknown

■

Back

pain

is

common

during

pregnancy;

compression

fractures

may

be

overlooked

■

Some

evidence

that

appendicular

fractures

may

be

more

common

1

■

Baseline

or

 pre-

pregnancy

bone

mineral

density

(BMD)

usually

unknown

■

May

be

due

to

a

combination

of

factors

shown

on

preceding

three

 slides

Recommend

(my

opinion):

■

Conservative

management

and

postpartum

investigations

into

bone

health

■

Expect

a

spontaneous

postpartum

increase

in

BMD

by

10-

20%

■

May

be

advisable

to

avoid

 breastfeeding

1

Herath

M.

Arch

Osteoporos

2017;

12:

86

Kovacs

CS

and

Ralston

SH.

Osteoporos

Int

2015;

26:2223-

2241

S

e

p

a

r

a

t

e

d

i

s

o

r

d

e

r

:

t

r

a

n

s

i

e

n

t

o

s

t

e

o

p

o

r

o

s

i

s

o

f

t

h

e

h

i

p

A

K

A

l

o

c

a

l

i

z

e

d

o

r

r

e

g

i

o

n

a

l

m

i

g

r

a

t

o

r

y

o

s

t

e

o

p

o

r

o

s

i

s

;

b

o

n

e

m

a

r

r

o

w

e

d

e

m

a

s

y

n

d

r

o

m

e

■

Not

due

to

systemic

resorption

of

the

 skeleton

■

A

form

of

chronic

regional

pain

syndrome

type

I

or

reflex

sympathetic

 dystrophy

■

Can

occur

equally in

men and

non-

pregnant

women

■

Women

present

during

the

third

trimester

or

early

postpartum

with

hip

pain,

limp,

or

hip

fracture;

occasionally,

both

hips

are

 involved

■

Radiographs

show

osteopenia

and

radiolucency

of

femoral

head

and

neck

■

DXA

shows

low

hip

BMD

whereas

spine

is

normal

or

not

as

reduced

■

MRI

shows

edema

of

femoral

head

and

marrow

■

DXA

and

MRI

findings

typically

resolve

within

2

to

12

months;

BMD

may

increase by

20-

40%

Kovacs

CS

and

Ralston

SH.

Osteoporos

Int

2015;

26:2223-

2241

L

a

c

t

a

t

i

o

n

L

a

c

t

a

t

i

o

n

■

Neonate

requires

an

average

of

210

mg

of

calcium

daily

through

milk

during

the

first

six

 months

■

Between

6

to

12

months

the

infant

requires

about

260

mg

of

calcium

 daily

■

120

mg

per

day

from

milk

■

140

mg

from

solid

foods

■

Nursing

twins

or

triplets

respectively

doubles

and

triples

the

maternal

calcium

output

■

Maternal

intake

and

absorption

of

calcium

is

typically

insufficient

to

meet

the

demands

of

milk

production

but

it

doesn’t

 matter

Kovacs

CS.

Physiol

Rev

2016;

96:449-

547

M

a

t

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n

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l

a

d

a

p

t

a

t

i

o

n

s

d

u

r

i

n

g

l

a

c

t

a

t

i

o

n

■

Temporary

loss

of

bone

mineral

to

provide

~210

mg

calcium

daily

to

milk

■

5-

10%

loss

of

BMD in 

2-

6

months 

for

women

■

trabecular

>

cortical

■

vertebral

>

appendicular

■

Renal

calcium

 conservation

■

Intestinal

calcium

absorption

is

normal

(non-

pregnant

rate)

Kovacs

CS.

Physiol

Rev

2016;

96:449-

547

G

r

e

a

t

e

r

d

e

c

l

i

n

e

i

n

B

M

D

w

i

t

h

l

o

n

g

e

r

d

u

r

a

t

i

o

n

o

f

l

a

c

t

a

t

i

o

n

More

C.

Osteoporos

Int

2001;

12:732-

737

R

a

n

d

o

m

i

z

e

d

i

n

t

e

r

v

e

n

t

i

o

n

:

1

g

r

a

m

o

f

s

u

p

p

l

e

m

e

n

t

a

l

c

a

l

c

i

u

m

d

o

e

s

n

o

t

p

r

e

v

e

n

t

l

a

c

t

a

t

i

o

n

a

l

b

o

n

e

l

o

s

s

Kalkwarf

H.

N

Engl

J

Med

1997;

337:523-

8.

Urine

Breast

Milk

Serum

Ca

++

Calcium

Intake

L

a

c

t

a

t

i

o

n

■

Serum

calcium

normal

■

Ionized

calcium

normal

or

slightly

increased

■

PTH

low

■

Calcitriol

normal

■

PTHrP

increased

■

Calcitonin

increased

for

first

six

weeks,

then

normalizes

■

Estradiol

low

■

Prolactin

elevated

Kovacs

CS

and

Kronenberg

HM.

Endocr

Rev

1997;

18:832-

872

Ca

2+

Ca

2+

Ca

2+

Ca

2+

Ca

2+

Ca

2+

Ca

2+



GnRH



LH,



FSH



E

2

,



PROG

PTHrP

Kovacs

CS.

J

Mammary

Gland

Biol

Neoplasia

2005;

10:105-

118

PTHrP

and

low

estradiol

(and

possibly

additional

factors)

drive

bone

resorption

during

lactation

B

r

a

i

n

,

b

r

e

a

s

t

a

n

d

b

o

n

e

c

i

r

c

u

i

t

O

T

P

R

L

C

T

CT

=

calcitonin

E

2

=

estradiol

OT

=

oxytocin

PRL

=

prolactin

PROG

=

progesterone

H

o

r

m

o

n

a

l

c

h

a

n

g

e

s

d

r

i

v

e

o

s

t

e

o

c

l

a

s

t

-

m

e

d

i

a

t

e

d

b

o

n

e

r

e

s

o

r

p

t

i

o

n

a

n

d

o

s

t

e

o

c

y

t

i

c

o

s

t

e

o

l

y

s

i

s

Ryan

BA

and

Kovacs

CS.

J

Clin

Invest

2019;

129:

3041-

3044

O

s

t

e

o

c

y

t

i

c

o

s

t

e

o

l

y

s

i

s

c

o

n

t

r

o

l

s

o

s

t

e

o

c

l

a

s

t

-

m

e

d

i

a

t

e

d

r

e

s

o

r

p

t

i

o

n

■

Osteocytes

express

enzymes

(cathepsin

K,

TRAP)

and

secrete

acid,

similar

to

osteoclasts

■

Loss

of

the

PTH

receptor

from

osteocytes

reduces

both

osteocytic

 osteolysis

and

osteoclast-

mediated

bone

resorption

■

Loss

of

cathepsin

K

from

osteocytes

reduces

osteocytic

osteolysis,

osteoclast-

mediated

bone

resorption,

and

osteoclast

number

■

Products

released

from

the

matrix

must

signal

to

osteoclasts;

without

them,

osteoclast

recruitment

and

activity

are

reduced

during

 lactation

Ryan

BA

and

Kovacs

CS.

J

Clin

Invest

2019;

129:3041-

3044

Lotinun

S.

J

Clin

Invest

2019;

129:

3058-

3071

Qing

H.

J

Bone

Miner

Res

2012;

27:

1018-

1029

C

a

l

c

i

t

o

n

i

n

a

c

t

s

a

s

a

b

r

a

k

e

o

n

b

o

n

e

r

e

s

o

r

p

t

i

o

n

d

u

r

i

n

g

l

a

c

t

a

t

i

o

n

(

a

t

l

e

a

s

t

i

n

m

i

c

e

)

Woodrow

JP.

Endocrinology

2006;

147:4010-

4021

K

e

y

p

o

i

n

t

s

a

b

o

u

t

l

a

c

t

a

t

i

o

n

■

The

neonatal

demand

for

minerals

in

milk

is

met

largely

by

maternal 

bone

resorption,

independent

of

dietary

calcium

intake

and

 absorption

■

Low

estradiol,

in

combination

with

high

circulating

concentrations

of

PTHrP

secreted

from

the

lactating

breasts,

stimulates

this

bone

 resorption

■

A

temporary

loss

of

maternal

bone

strength

is

inevitable

during

lactation,

but

for

most

women

this

happens

silently

with

no

consequences

C

a

u

s

e

s

o

f

s

k

e

l

e

t

a

l

f

r

a

g

i

l

i

t

y

a

s

s

o

c

i

a

t

e

d

w

i

t

h

l

a

c

t

a

t

i

o

n

Hormonal

■

Normal

or

even

excess

lactational

bone

loss,

mediated

by

PTHrP

and

low

estradiol*

Other

■

Increased

breast

milk

output

(e.g.,

nursing

twins)

■

Prolonged

duration

of

exclusive

lactation

■

Being

a

primipara

Mechanical

■

Carrying,

bending,

and

lifting

maneuvers

with

baby

and

related

paraphernalia

All

of

the

factors

previously

listed

for

pregnancy,

plus:

*This

PTHrP-mediated

skeletal

resorption

is

sufficient

to

cause

hypercalcemia

in

some

normal

breastfeeding

women,

and

to

normalize

calcium

homeostasis

in

hypoparathyroid

women

while

breastfeeding

Kovacs

CS

and

Ralston

SH.

Osteoporos

Int

2015;

26:2223-

2241

O

s

t

e

o

p

o

r

o

s

i

s

d

u

r

i

n

g

l

a

c

t

a

t

i

o

n

■

Occasionally

vertebral

crush

fractures

occur

during

lactation

■

Sometimes

it’s

a

cascade

of

6

to

10

spontaneous

crush

fractures,

and

these

cases

get

reported

in

the

literature;

it’s

unknown

how

common

1

or

2

fractures

might

be

■

Back

pain

is

common

 post-

partum;

compression

fractures

may

be

missed

■

Prepregnancy

(baseline)

bone

density

is

usually

 unknown

■

Likely

due

to

bone

loss

during

lactation

on

top

of

skeletal

losses

or

 inherent

fragility

that

preceded

this

time

 period

■

70-

90%

of 

reproduction-

associated

fractures

occur within

2-

3

months

of 

lactation

Recommend

(my

opinion):

■

Conservative

management

with

expectation

that

bone

mass

will

increase

 after

weaning;

hold

off

on

use

of

osteoporosis

medications

■

Spontaneous

BMD

increases

of

10-20%

and

up

to

40%

have

occurred

■

Reserve

pharmacotherapy

for

inadequate

responders

or

more

severe

cases

Kovacs

CS

and

Ralston

SH.

Osteoporos

Int

2015;

26:2223-

2241

E

s

t

i

m

a

t

e

s

o

f

i

n

c

i

d

e

n

c

e

o

f

o

s

t

e

o

p

o

r

o

s

i

s

o

c

c

u

r

r

i

n

g

i

n

a

s

s

o

c

i

a

t

i

o

n

w

i

t

h

p

r

e

g

n

a

n

c

y

o

r

l

a

c

t

a

t

i

o

n

■

Of

1,260

thoracic,

lumbar,

or

thoracolumbar

MRIs

done

in

women

of

reproductive

age

over

2

years

at

one

institution,

six

women

(0.47%)

had

compression

fractures

associated

with

recent

pregnancy

or

lactation

1

■

Mean

of

5.6

compression

fractures

per

woman

■

Of

837,347

recent

pregnancies,

379

women

(4.5

/

10,000)

presented

to

hospital

within

2

years

due

to

 fractures

2

■

The

diagnosis

was

delayed

12

weeks

from

the

onset

of

pain

in

most

 women

3

■

Explained

away

as

normal

back

pain

expected

during

lactation

1

Yildiz

AE.

Osteoporos

Int

2022;

32:981-

989

2

Toba

M.

J

Bone

Miner

Metab

2017;

40:748-

754

3

Kondapalli

AV.

Osteoporos

Int

2023;

34:1477-

1489

W

h

e

r

e

d

o

t

h

e

c

o

m

p

r

e

s

s

i

o

n

f

r

a

c

t

u

r

e

s

o

c

c

u

r

?

Hadji

P.

Geburtshilfe

Frauenheilkd

2022;

82:619-

626

Number

and

location

of

fractures

in

47

cases

followed

between

2006

and

2018

at

one

institution

in

Germany

P

o

s

t

-

w

e

a

n

i

n

g

b

o

n

e

r

e

c

o

v

e

r

y

P

o

s

t

-

w

e

a

n

i

n

g

s

k

e

l

e

t

a

l

r

e

c

o

v

e

r

y

■

Return

to

baseline

BMD

and

presumed

bone

strength

in

six

to

twelve

 months

for

most

women

■

However,

there

are

persistent

changes

in

appendicular

microarchitecture

seen

by

HR-

pQCT

at

the

radius

and

tibia

(cannot

examine

spine

and

hip

by

this

technique)

1,2

■

Regulation

of

skeletal

recovery

is

not

understood

■

In

the

 long-

term,

a

history

of

lactation

has

a

neutral

or

protective

effect

 against

the

development

of

low

BMD,

osteoporosis,

and

fragility

 fractures

1

Brembeck

P.

J

Clin

Endocrinol

Metab

2015;

100:535-

543

2

Bjornerem

A.

J

Bone

Miner

Res

2017;

32:681-

687

Kovacs

CS.

Physiol

Rev

2016;

96:449-

547

E

p

i

d

e

m

i

o

l

o

g

y

o

f

p

a

r

i

t

y

,

l

a

c

t

a

t

i

o

n

,

a

n

d

o

s

t

e

o

p

o

r

o

s

i

s

■

More

than

six

dozen

epidemiological

studies

have

found

that

parity

or

lactation

(or

both)

have

a

neutral

or

protective

effect

on

long-

term

risk

of

 osteoporosis,

fragility

fractures,

or

low

BMD

■

A

study

of

1,852

twins

and

their

female

relatives,

including

83

twins

who

were

discordant

for

pregnancy

and

lactation,

found

no

effect

of

breastfeeding

 history

on

BMD

■

Parous

women

who

had

breastfed

had

higher

BMD

than

parous

women

who

had

never

breastfed

Paton

LM.

Am

J

Clin

Nutr

2003;

77:

707-

714

Kovacs

CS.

Physiol

Rev

2016;

96:449-

547

Segal

E.

Osteoporos

Int

2011;

22:2907-

2911

L

a

c

t

a

t

i

o

n

a

l

B

M

D

d

e

c

l

i

n

e

i

s

f

o

l

l

o

w

e

d

b

y

p

o

s

t

-

w

e

a

n

i

n

g

r

e

c

o

v

e

r

y

Sowers

MF.

JAMA

1993;

269:

3130-

3135

L

a

c

t

a

t

i

o

n

a

l

B

M

D

d

e

c

l

i

n

e

i

s

f

o

l

l

o

w

e

d

b

y

p

o

s

t

-

w

e

a

n

i

n

g

r

e

c

o

v

e

r

y

Kalkwarf

HJ.

Obstet

Gynecol

1995;

86:26-

32

S

p

o

n

t

a

n

e

o

u

s

B

M

D

i

n

c

r

e

a

s

e

i

n

w

o

m

e

n

w

h

o

f

r

a

c

t

u

r

e

d

1

3

w

o

m

e

n

a

t

a

c

e

n

t

e

r

i

n

t

h

e

U

K

Phillips

AJ.

Osteoporos

Int

2000;

11:449-

454

B

o

n

e

r

e

c

o

v

e

r

y

a

f

t

e

r

l

a

c

t

a

t

i

o

n

i

n

v

o

l

v

e

s

…

■

Stimulation

of

new

bone

formation

■

Remineralization

of

existing

bone

around

 osteocytes

■

Compensatory

increase

in

diameter

of

some

long

bones?

Kovacs

CS

and

Ralston

SH.

Osteoporos

Int

2015;

26:2223-

2241

W

h

a

t

r

e

g

u

l

a

t

e

s

p

o

s

t

-

l

a

c

t

a

t

i

o

n

s

k

e

l

e

t

a

l

r

e

c

o

v

e

r

y

?

■

In

animal

models,

none

of

the

known

calciotropic

hormones

(“the

 usual

suspects”)

are

required

for

full

skeletal

recovery

(bone

mass

and

 strength)

■

Includes

PTH,

calcitriol,

VDR,

PTHrP,

calcitonin,

estradiol

■

Limited

case

reports

support

these

findings,

such

as

a

documented

40%

increase

increase

in

bone

mass

after

weaning

in

an

aparathyroid

 woman

Segal

E.

Osteoporos

Int

2011;

22:2907–2911

Kovacs

CS.

Physiol

Rev

2016;

96:449-

547

B

o

n

e

m

i

n

e

r

a

l

c

o

n

t

e

n

t

(

B

M

C

)

r

e

c

o

v

e

r

s

w

i

t

h

o

u

t

P

T

H

Kirby

BJ

J

Bone

Mineral

Res

2013;

28:1987-

2000

S

p

o

n

t

a

n

e

o

u

s

a

n

d

p

o

s

t

-

p

h

a

r

m

a

c

o

t

h

e

r

a

p

y

b

o

n

e

r

e

c

o

v

e

r

y

■

Individual

case

reports

and

series

have

documented

spontaneous

BMD

increases

of

 10-

20%

(one

case

up

to

40%)

■

Pharmacotherapy

has

been

used

in

case

reports

and

series,

with

 reported

BMD increases of

10-

30%