Dr.Eslam Osteoporosis Lec.1 part.

1. Bisphosphonates

Alendronate, Risedronate, Ibandronate, Zoledronic acid

 They inhibit normal and abnormal bone resorption.
 First-line therapy (men & postmenopausal women),
Exception: Ibandronate second-line therapy.

Reduces vertebral and nonvertebral fractures (Exception:

Efficacy ibandronate reduces only vertebral fractures).

 Hypocalcemia: correct prior to therapy; ensure adequate

calcium and vit. D intake [concomitantly with the course of
therapy].

 Abnormalities of esophagus
(Oral bisphosphonates ↑esophagitis, esophageal erosions and
strictures; risk is higher in patients non-adherent to use
Contraindications instructions).

 Inability to stand or sit upright for 30 minutes

(sit or stand upright for at least 30 minutes after
administration to reduce esophageal side effects).

 Oral bisphosphonates should be taken with plain water only,

not coffee, juice, or mineral water
(polyvalent cations → ↓ absorption [non-absorbable complex]).

 Wait at least 30 minutes after taking bisphosphonate before

taking any medications, food, or drinks except for water.

Exception  With ibandronate, must wait 60 minutes.

 (Risedronate sodium, delayed release) must be taken with food

 Recommendations: in case of Crcl< 30 ml/min, find an alternative or adjust the dose.

 Duration: not more than 5 years, may be extended to more 3 years( If has good BMD)

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2. Denosumab

It is approved for postmenopausal women with osteoporosis and for men and women
with bone loss associated with prostate or breast cancer

((similar to OPG in the mechanism))

MOA  It inhibits osteoclast-mediated bone resorption, monoclonal antibody

against receptor activator of nuclear factor қ β ligand (RANKL),
cytokine essential for formation, function, survival of osteoclasts.

 Considered alternative first-line therapy

Efficacy ↓ risk of spinal and hip fractures.
[vertebral and non-vertebral fractures]

Safety  Has immunosuppressive effect. So, facilitates Possible opportunistic

issues infections, skin infections such as cellulitis.(as monoclonal AB).
 Hypocalcemia: Patients should take calcium and vitamin D together
with denosumab.
 No need for dose adjustment in case of impaired renal function.
Contraindicated in pregnancy

 Ca+2 supplement:
 It is a supportive ttt, to maintain normal calcium concentration and prevent
hypocalcemia associated with other drug treatments for osteoporosis.

 Elemental calcium intake: Avoid doses higher than 2500 mg/day:

Higher doses may increase risk of constipation, contribute to kidney stones,
and inhibit absorption of zinc or iron.

 Vit. D:
 it is supplementary that Promotes calcium reabsorption.
 Goal: 20 ng/mL.
 (vitD+CA+2 can be used in osteopenic patient as supplement to avoid
osteoporosis occur)

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3. Selective estrogen receptor modulators

(Raloxifene)
 Prevention and treatment of osteoporosis in postmenopausal women only.

Selective estrogen receptor modulator [agonist on est. receptors in

MOA bone&antagonist at breast receptors].
• ↓ Bone resorption. • ↓ Overall bone turnover.

Efficacy • ↓ The risk of vertebral fractures.

• ↓ Total cholesterol and LDL-C; does not reduce risk of CHD.

• ↑ Risk of DVT and PE (black box warning, discontinue 72 hrs

Contraindications prior to and during prolonged immobilization).
• ↑ Risk of death due to stroke in postmenopausal women with
CHD black box warning.
• Pregnancy and lactation
 -Ospemifene(synergism)
 Cancer except breast and
Conjugated estrogens and bazedoxifene

Indication: Prevention of osteoporosis in postmenopausal women.

Conjugated Mechanism: Selective estrogen receptor modulator plus estrogen.
estrogens and Efficacy: ↓ risk of vertebral and non-vertebral fractures.
bazedoxifene Contraindications:
• Similar to those of raloxifene.
• Avoid additional estrogens (black box warnings).
• dementia in women > 65 y old (black box warnings).
• Estrogens should be prescribed at the lowest effective doses and
for the shortest duration consistent with treatment goals and risks for
the individual woman
. • Breast cancer and estrogen dependent neoplasia.
• Hepatic impairment.
Metabolized by (cyp3A4) so inducers or inhibitors of
3A4 may affect estrogen level

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Dr.Eslam Osteoporosis Lec.1 part.1

4. Teriparatide & Abaloparatid

Recombinant human PTH [PTH analogue] #why?

 Cause fluctuation in PTH conc.
 Has inhibitory effect on sclerostin. (A protein increases osteoclast activity &
decrease that of osteoblast).

It regulates bone metabolism, intestinal calcium absorption, and renal tubular calcium
and phosphate reabsorption

 Reserved for treating women at high risk of fracture and men,

Efficacy including those with very low BMD (T-score lower than –3.0)
and a previous vertebral fracture (highly effective).

 ↓ Vertebral fractures and non-vertebral fractures; not ↓ hip

fractures.
↑ risk of osteosarcoma, especially in women (postmenopausal)
Contraindications (Those with paget disease, open epiphysis or previous external
beam or implant radiation therapy involving skeleton).

5. Sclerostin inhibitor, a factor in bone regulation, helps build bone and

Romosozumab decreases bone resorption. *↑ by glucocorticoids, ↓by sex hormones and
( monoclonal PTH]
AB) Indicated: for postmenopausal women who are at high risk of fracture or
when other osteoporosis treatments have failed. [Effective against
vertebral fractures]
C.I: in case of -myocardial infarction. -stroke.
6. Calcitonin- Inhibition of bone resorption.
salmon Used for treatment of osteoporosis in women > 5 years postmenopause.
Not a first-line drug; useful for bone pain caused by vertebral compression
fractures.
Efficacy: Nasal calcitonin ↓ risk of vertebral fractures, rapid onset
(emergency use).
7. Testosterone for men & estrogen for women
Hormone
therapy:

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Dr.Eslam Osteoporosis Lec.1 part.1

Treatment of postmenopausal
women

High risk and no prior fractures

Alendronate.
Assess adherence
Denostunab.
Change to injectable
Risedronate. Drug holiday after 5 yr of PO or 3 antiresorptive
)yr of IV therapy)
)if on PO(
Zoledronate. ,Resume therapy with a fracture
If on injectable or at very
BMD declines, BTM rises to high

Ibandronate. pretreatment value. risk, change to

.abaloparatide
Raloxifene.
romosozumab, or
teriparatide
Very high risk and prior fractures:
First line Alternative
Denosumab-continue until no longer high risk; Alendronate, risedronate
transition to another antiresorptive agent
Romosozumab x 1 yr - sequential therapy with PO
or injectable antiresorptive agent
Abaloparatide or teriparatide x 2 yr-sequential
therapy with PO or injectable antiresorptive agent
Zoledronate x 6 yr (if stable)- if progressive bone
loss or recurrent fractures change to abaloparatide,
teriparatide, or romosozumab.

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