Rheumatology

Internal medicine
Fourth Grade
Semester 9

Faculty of Medicine
Tanta University
 OSTEOPROSIS

By Dr/ Thanaa Farag Mansour

Lecturer of Internal Medicine
Rheumatology & Immunology unit
Tanta University
2022
 Lecture ILOs/ Objectives:
• By the end of this lecture the student will be
able to:
1.Describe osteoporosis and its different types
2.Describe risk factors of osteoporosis.
3. Describe osteopenia
4.Diagnosis of osteoporosis
5.Prevention and treatment of osteoporosis.
 Osteoporosis
(Fragile Bone)

Definition
• Progressive skeletal disease characterized by Low bone
mass and microarchitectural disruption causing
weakening of bone which predisposes to fractures.
• Osteoporosis comes from ‘osteo’ meaning bone and the
greek word por (passage) ie. simply it means porous
bone.
• Brittle bone” disease
• The underlying mechanism in osteoporosis is an
imbalance between bone resorption and bone formation.
• Bone strength reflects the integration of bone mass and
 Epidemiology

•Age. Osteoporotic fractures are more common with increasing age. The annual
UK incidence of hip fractures is 4.3/100 000 women aged 45–64 years, rising to
90.1/100 000 women aged 75–85 years.

Sex. Osteoporotic fractures are more common in women than men (about 70%
occur in women).

Genetics. There may be a family history, and twin studies suggest a significant
genetic component.

Geography. Osteoporosis is most common in developed countries.

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 Pathophysiology
unhealthy bone remodeling

1.Bone loss occurs when bone resorption > bone formation,

leading to high bone turnover and decrease bone mineral density
(BMD).
2.Failure to reach a normal peak bone mass

3.In addition, the increased quantity of immature bone that is not

adequately mineralized leading reduced bone quality and
structural integrity are impaired.

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 Normal bone vs. Osteoporotic bone

• The normal bone shows a pattern of

strong interconnected plates of bone.

• Much of this bone is lost in

Osteoporosis and the remaining
bone has a weaker rod-like structure
& some of the rods are completely
disconnected.
 Clinical Findings
• Generally patients are asymptomatic
even with very low bone densities

• Acute and chronic pain in the elderly

is often due to osteoporotic fractures.

• A traumatic or low impact fractures

called fragility fractures.

• Bones involved are the vertebral

• column, ribs, hip and wrist.
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 Clinical Findings
• The symptoms of a vertebral
collapse (compression fracture)
are back pain, shooting pain
due to nerve root compression.

• Multiple vertebral fractures

• Lead to a stooped posture,
kyphosis, loss of height,
with resultant reduction in
mobility.
 Risk Factors: non-modifiable
• Age (increasing)

• Sex : female more than male

• Low BMI (small, low weight;< 58 kg , BMI (<19

kg/m2) )
• Ethnicity: Caucasian > Asian/Latino > African
American
• Family History of Fracture
 Risk Factors: Modifiable
• Medications:
 Corticosteroid therapy (doses of prednisolone > 7.5 mg
daily for greater than 2 months; any dose of glucocorticoid
in the elderly > 65 yrs).
 Chronic anticonvulsant therapy
 Prolonged use of heparin.
 Proton pump inhibitors
 Treatments for certain malignancies e.g breast cancer,
prostate cancer( hormonal or chemotherapy).
• Rheumatoid Arthritis
• Eating disorders (Anorexia nervosa, Bulimia).
• Organ transplant recipients.
 Primary osteoporosis • Secondary osteoporosis
• Juvenile osteoporosis. • Congenital
• Idiopathic osteoporosis • Diet
• Postmenopausal • Drugs
osteoporosis • Endocrine disorder
• Age-related, or senile, • Other Systemic Disorder
osteoporosis
 Secondary Osteoporosis
With risk factors
Pharmacotherapy:

• Glucocorticoids
• Thyroxine.
• Anticonvulsants (phenytoin, phenobarbital)
• Lithium, aluminium
• Heparin (long-term)
• Drugs producing hypogonadism (aromatase inhibitors, antimetabolite
chemotherapy, medroxyprogestrone, gonadotropin-releasing hormone
agonists)
Endocrine Disorders:
• Cushing syndrome
• Hyperparathyroidism
• Hypogonadism
• Hyperthyroidism
Gastrointestinal disorders:
• i. Alcohol abuse related diseases
• ii. Malabsorption syndromes
• iii. Eating disorders
• iv. Celiac disease
• v. Inflammatory bowel diseases
• vi. Chronic liver diseases
• vii. Gastrectomy

Genetic diseases:
• i. Osteogenisis imperfecta
• ii. Hypophosphatasia

Miscellaneous causes:
• i. Organ transplant
• ii. Rheumatoid arthritis
• iii. Neurological diseases
• iv. Spinal cord injury
• v. Multiple sclerosis
• vi. Prolonged bed rest
• vii. Multiple myeloma
• viii. Marrow infiltrative diseases
 Diagnosis
Secondary Osteoporosis
Clinical features:
o Low back ache which radiates around the trunk Or
down the limbs.
o Loss of height and appearance of thoracic kyphosis.
o Patient appears older than his or her years.
o History of Fractures.
o Hepatosplenomegaly (systemic disease)
o Skin pigmentation (Cushing's synd.)
 Secondary Osteoporosis

Standard Laboratory Tests

• CMP (creatinine, calcium, alkaline phosphatase)
• Creatinine: assess for renal function for
choice of treatment
• Calcium:
• if too low consider cause and replete
• If too high consider hyperparathyroidism

• High Alkaline phosphatase: osteomalacia or Paget’s disease

 Secondary Osteoporosis

Standard Laboratory Tests

• 25-OH Vitamin D
• Important to replete if low (low vit D can lead to
elevated PTH)
• 24-hour Urine calcium
• High - Urine calcium (>300mg/day): male
osteoporosis, granulomatous disease or malignancy with
increased bone turnover
• Low - Urine calcium(<50mg/day): osteomalacia,
malnutrition, malabsorption
 Secondary Osteoporosis

• Additional Laboratory Tests

• PTH (with calcium & phosphorus)
• If calcium is elevated
• If considering using teriperatide (Forteo)
• Patients with ESRD
• SPEP/UPEP with immunofixation
• In patients with fragility fracture
• Consider in patients to be placed on teriperatide (Forteo)
• Testosterone
• In men with osteoporosis
• 24 hour urine cortisol
• In patients with cushinoid features and unexpected osteoporosis
• Thyroid function tests (TSH,FT3,FT4)
 Vertebral Imaging
X-ray of dorso-lumbar spine
1. Anterior wedging of one or
more vertebrae with vertebral
collapse, vertebral end-plate
irregularity, and general
demineralization.
2. Posterior wedging is
uncommon and may indicate
an underlying destructive
lesion.
Vertebral Fracture- x-ray
 Vertebral Imaging
CT
determining potential instability of a wedge fracture .

MRI
indicate severity and acuity of a fracture, exclude
underlying malignancy
 What is BMD
• A TEST?
bone mineral density test is an easy,
reliable test that measures the density or
thickness of bones. It measures the amount
of mineral matter (calcium) per square unit
area of bone.
There are several different ways to measure BMD
1.Dual-energy X-ray absorptiometry (DEXA)
2.Peripheral dual-energy X-ray absorptiometry (P-DEXA).
 Dual-energy X-ray absorptiometry
(DEXA)

• This is the most accurate

• and standardized way to measure
• BMD.
• It uses two different X-ray beams to estimate bone
density in the spine and hip.
• It is a quick,easy and painless test where nothing is
injected or swallowed.
• A low-dose x-ray is taken which is is only 10% of the
radiation exposure of a chest x-ray.
 Groups That Should Be
Tested With DXA
• ALL women age >65 and ALL men >70
• Post menopausal women and men 50-70 with risk factors
• Men with hypogonadal conditions
• All individuals over the age of 50 with Low trauma
fracture
• All individuals who are taking long term
corticosteroids(7.5mg of prednisone daily for 3mnths)

• Patients with diseases associated with bone loss and

fracture e.g hyperparathyroidism
• Patients with height loss >1.5 inches
• Radiographic evidence of osteopenia
 BMD Interpretation
• Results are generally scored by two measures,
 T-score
 Z-score.
T-Score is the BMD at the site when compared to the young
normal reference mean. Used to diagnose osteoporosis and
whether treatment is required in Postmenopausal women
and men.

• Negative scores indicate lower bone density, and positive scores

indicate higher bone density.
 T-SCORE

The T score compares your bone

density with that of healthy young adult.

• A score of 0 means your BMD is equal to the standard for

a healthy young adult.

• Differences between your BMD and that of the healthy young

adult standard are measured in units called standard deviations

(SDs).

• The more standard deviations below 0, indicated as negative

numbers, the lower your BMD.
 As shown in the table below,

• A T-score between +1 and −1 is considered normal or healthy.

• A T-score between −1 and −2.5 indicates that low bone mass
(Osteopenia).
• A T-score of −2.5 or lower indicates osteoporosis.
• The greater the negative number, the more severe
the osteoporosis.
Osteoporosis
Management
 Reducing pain and deformity, and
improving quality of life
 Optimize and stabilize bone mass
 Reduce the future incidence of
osteoporosis
 Improving functional capacity and
mobility
 Identify risk factors for developing
osteoporosis and resolve reversible
risks.
 PREVENTION
 Exercise such as walking, running regularly.
 Avoid smoking, it can reduce the levels
of estrogen and increase bones Loss.
 Avoid excessive alcohol. It increases bone resorption by
increasing RANKL and decreases bone formation by increasing
oxidative stress.
 Avoid caffeine, because excessive caffeine consumption
increases calcium excretion, Hypophosphatemia
 Prevention of fall : Ambulation-assistive devices (canes and
walkers) and Assistance
Non pharmacologic treatment
Diet changes : For all individuals, a
well-balanced diet with adequate
calcium and vitamin D is essential for
healthy bones.
Calcium contributors - Dairy
products like milk, yogurt, cheese,
ice cream, cottage cheese, and
fortified orange juice or soy products.
Most vitamin D comes from sun-
induced skin conversion
Vitamin D contributors - fatty fish,
few unfortified foods
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 Vitamin D3
Vitamin D deficiency results from insufficient intake, decreased
sun exposure, decreased skin production, decreased liver and
renal metabolism
 Vitamin D and PTH work together to maintain calcium
homeostasis. Supplemental vitamin D maximizes intestinal
calcium absorption and has been shown to increase BMD
 Dose: 200–1000 units/day.
 Usually found as alone or combination with calcium or as
alfacalcidol “Bone one®”(vitamin D precursor)

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 Calcium
 Taken in adequate amounts to prevent bone destruction. Usually
combined with vitamin D and osteoporosis medications
 Calcium carbonate (Calcimate®) is the salt of choice because it
contains the highest concentration of elemental calcium (40%)
and is the least expensive. It should be ingested with meals to
enhance absorption from increased acid secretion.
 Calcium citrate or acetate: absorption is acid independent and
need not be taken with meals.
 SE: Constipation
treated with increased water intake, and
dietary fiber
 Recommended Calcium Intake

• From diet and supplements

combined: 1200 mg daily
• Maximum single doses of 600 mg or less of
elemental calcium are recommended

• Evidence shows a benefit of

calcium on reduction of fracture
risk
 FDA-Approved
Osteoporosis Medications
Antiresorptives Anabolics
• Estrogen/HRT* Osteogenic drugs
• Bisphosphonates
– Alendronate (Fosamax)* • Parathyroid Hormone
– Risedronate (Actonel)* (Teriparatide, Forteo)
– Ibandronate (Boniva) • PTHrP Analogue
– Zoledronic Acid (Reclast)* (Abalopartide, Tymlos)*
• SERMS(Selective estrogen • Romosozumab(Evenity)
receptor modulators):
– Raloxifene (Evista)
• Calcitonin (Miacalcin)
• Denosumab(Prolia)*
*reduces non vertebral fracture
 Bisphosphonates
(Dronates)

• BPN therapy should be considered first line therapy for the

treatment of osteoporosis, in conjunction with lifestyle
modifications and appropriate doses of calcium plus Vit-D.
• for the prevention and treatment of postmenopausal
osteoporosis. Binds to bone, inhibits osteoclast activity

• 1st generation : Etidronate and Tiludronate.

• 2nd generation : Alendronate (Fosamax, Bonapex),
Pamidronate(Aredia) & Ibandronate (Boniva, Bonaprove).
• 3rd generation : risedronate (Actonel), and Zoledronate
(Zometa,Aclasta)
 Contraindications
• Documented hypersensitivity.
• Inability to stand or sit upright for at
least 30 min.
• Hypocalcemia.
• Esophageal abnormalities (eg,
stricture, achalasia) that might delay
esophageal emptying.
• Pregnancy: category C.
• Cannot be used with eGFR < 30-35%
 DENOSUMAB (PROLIA):
(RANK Ligand Inhibitor )
• Human monoclonal IgG2 antibody (Denosumab ) that has high
affinity for RANKL and blocks the binding of RANKL to
RANK, prevent formation of active osteoclasts. Inhibits bone
resorption.
• Indicated for: prevention of fracture in postmenopausal
women with osteoporosis and high fracture risk (ie, history
of osteoporotic fracture, failed other treatments).
•
 DENOSUMAB (PROLIA):
(RANKL Inhibitor )
• Dosing: The product is available as a refrigerated prefilled pen
or single-use vial administered subcutaneously
• 60 mg SC every 6 monthes for 36 months (3 years). Increased
BMD at all skeletal sites and decreased bone turnover markers at
24 months.
 Denosumab (Prolia):
• Adverse effect : Denosumab was generally well tolerated.
• Dysregulation of the immune system, potentially leading to infection or
malignancy
• AVN of Jaw.
• Suppression of bone turnover (delayed fracture healing)
• Atypical fragility fractures.

• Contraindications:
 Hypocalcemia

 Pregnancy

 Hypersensitivity

No dosage adjustment is necessary in renal

impairment
Parathyroid Hormone Therapy
Mechanism of Action:
• Stimulates bone remodeling by increasing bone formation
• Parathyroid hormone (PTH) was approved by the FDA in 2002
for the treatment of osteoporosis in postmenopausal women and
men.
• Relatively low doses activate parathyroid hormone receptors in
bone to produce anabolic effects that stimulate new bone
formation with the net effect of increased bone mass and
improved skeletal microarchitecture. when it is administered
intermittently in low doses.
 Parathyroid Hormone Therapy
(PTE) : (Abaloparatide, Teriparatide)

• The recombinant human parathyroid hormone, teriparatide,

Abaloparatide, is administered as a once-daily subcutaneous
injection and is approved for use for up to 24 months (not
more than 2 years).
• The initial dose should be given lying or sitting to avoid
orthostatic hypotension
Parathyroid Hormone Therapy
• Adverse effects : dizziness, syncope ,
leg cramps & hypercalcemia , hypercalciuria
• Contraindications:
• Hypercalcemia
• Multiple Myeloma,
• Bone metastasis , skeletal tumor, or those who have had
skeletal irradiation.
• (hyperparathyroidism).

• Pregnant &breastfeeding .
 Hormone Replacement Therapy:

Estrogens +/- progesterones

• HRT was once considered to be the primary therapy of
osteoporosis prevention/treatment
• Currently, HRT is not used to treat or prevent osteoporosis
alone (often used for other indications such as severe
postmenopausal symptoms, mainly for the control of
vasomotor symptoms.

Side effects : increased risk for breast cancer,

cardiovascular disease, thrombosis…
 Estrogen
Agonist/Antagonist
• Estrogen agonists
(eg. antagonists
Raloxifene) (known previously as
selective estrogen receptor modulators or SERMs)
which differ from estrogen biochemically and
structurally but can act as estrogen agonists or
antagonists depending on the specific target tissues.
• Raloxifene) (Evista) :Indication: prevention of
osteoporosis in post menopausal women.
• Dose: 60mg tab once daily
 Estrogen Agonist/Antagonist

Less effective than bisphosphonates, After

discontinuation, the beneficial effect is lost
and bone loss returns
• Adverse effects
• Increased risk of venous thrombosis(DVT
and stroke risk) .
• Hot flashes and leg cramps and edema
• A flulike syndrome
 Calcitonin(micalcic) Therapy
• Calcitonin is an endogenous peptide hormone secreted by the
thyroid gland .
• Calcitonin acts directly to reduce bone resorption by binding to
specific receptors of the osteoclast.
• Salmon calcitonin (synthetic peptide form of calcitonin )is used
for treatment of osteoporosis because it is more potent and has a
longer duration of action than human calcitonin.
• It acts quickly in the treatment of osteoporosis.
 Calcitonin(micalcic) Therapy
Dose & Indications
1. Treatment of postmenopausal osteoporosis: Especially
in patients in whom bisphosphonates and
estrogen are contraindicated or not tolerated.
2. Analgesic effect: for patients who have acute painful vertebral
fractures.
3. Paget's disease and Hypercalcemia
3. Not approved for prevention or for use in glucocorticoid-
induced osteoporosis.
 Calcitonin(micalcic) Therapy
 Efficacy:
 Less effective than other treatments (third line)
 Helpful in reducing pain from fractures of spine mainly.
it should be prescribed for short-term treatment (4
weeks)
 BUT not reduce hip fractures

 Side effect:
 Nasal irritation (congestion, discharge, or sneezing).
 Calcitonin has been linked to an Increased risk of
cancer
Guidelines of ACR
Supplementation of calcium + vitamin D
1 First line biphosphonate and denosumab

Second line teraparatide, Ibandronate,

2 or raloxifene

Third line intranasal calcitonin

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 Response to therapy
• There are no definite guidelines as to
when or if to repeat DEXA scans with
treatment.
• For patients on pharmacotherapy, it is
typically performed 2 years after
initiating therapy on the same
machine and every 2 years thereafter;
however, more frequent testing may
be warranted in certain clinical
situations.
Resource & References
1. Allen S, Forney-G A, Homan M, et.al. Diagnosis
and Treatment of Osteoporosis. ICSI.2017:1-45.
2. Kristie NT, Janette DL, Chew KV, et al.
Osteoporosis: A Review of Treatment Options.
P&T.2018; 43(2): 92–104.
3. Jeremiah MP, Unwin BK, Greenawald MH, et al.
Diagnosis and management of osteoporosis. Am Fam
Physician. 2015;92(4):261–268.
4. Gallagher JC, Shi H, Mirkin S, et al. Changes in
bone mineral density are correlated with bone
markers and reductions in hot flush severity in
postmenopausal women treated with bazedoxifene/
conjugated estrogens. Menopause.
2013;20(11):1126–1132.
GOOD LUCK & THANK YOU