Professional Documents
Culture Documents
Referat Osteoporosis
Referat Osteoporosis
Disusun Oleh:
Ahmad Marzuqi bin Abdullah
112015434
Pembimbing:
dr. Arsanto Triwidodo, SpOT(K) MHKes
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CHAPTER I
INTRODUCTION
Osteoporosis is a systemic metabolic bone disease that is characterized by the
reduction in bone mass density. It is due to reduced bone mineral and matrix and
accompanied by the destruction of micro-architecture in the bone tissues. With consequent
decrease in bone strength, this will result in a higher tendency of becoming brittle bones.
Formation and bone resorption are mostly in balance in individuals aged around 30-40
years. The imbalance of bone resorption happened to start when women reach menopause
and men reach the age of 60 years.
Osteoporosis causes more than 8.9 million fractures each year in the world, with 4.5
million cases occur in the United States and Europe. Currently there are approximately 0.3
million hip fractures per year in the United States and 1.7 million in Europe. Almost all of
these events is associated with osteoporosis, whether primary or secondary. The ratio of
women and men in hip fracture is about 2 : 1. The incidence of wrist fractures in England and
America ranges from 400-800 per 100,000 women. Vertebral compression fracture is much
more difficult to predict because it is often asymptomatic. It is estimated that more than one
million American postmenopausal women will suffer a fracture of the spine in the course of
one year.
This literature was made to discuss about the pathogenesis, diagnosis and
management of osteoporosis which are often found in the advanced process. It is expected to
broaden our knowledge of us all in the early diagnosis and proper treatment of osteoporosis.
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CHAPTER II
DISCUSSION
2.1 Definition
The word osteo literally means bone and the word porosis means cavities.
Osteoporosis is a systemic skeletal disease characterized by low bone mass and deterioration
of bone tissue microarchitecture resulting in bone fragility and an increased susceptibility to
fractures. National Institute of Health (NIH) proposed a new definition of osteoporosis as a
systemic skeletal disease characterized by compromised bone strength until the bones can
easily be broken. Operationally osteoporosis is defined based on the bone mineral density
(BMD) values. Based on WHO criteria, osteoporosis is when BMD values are at 2.5 standard
deviations (SD) or below the average value of healthy young adults (T score <-2.5 SD).1
Definition Criteria
Normal BMD > -1 SD
Low bone mass
BMD is between -1SD and -2.5 SD
(osteopenia)
Osteoporosis BMD is below -2.5 SD
Severe osteoporosis BMD is below -2.5 SD and with bone fractures
2.2 Epidemiology
Most studies assessing the prevalence and incidence of osteoporosis use the rate of
fracture as a marker for the presence of this disorder, although BMD also relates to risk of
disease and fracture. The risk of new vertebral fractures increases by a factor of 2-2.4 for
each standard deviation (SD) decrease of BMD measurement. Women and men with
metabolic disorders associated with secondary osteoporosis have a 2- to 3-fold higher risk of
hip and vertebral fractures.2
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Risk for osteoporosis increases with age as BMD declines. Senile osteoporosis is most
common in persons aged 70 years or older. Secondary osteoporosis, however, can occur in
persons of any age. Although bone loss in women begins slowly, it speeds up around the time
of menopause, typically at about or after age 50 years. The frequency of postmenopausal
osteoporosis is highest in women aged 50-70 years.2,3
The number of osteoporotic fractures increases with age. Wrist fractures typically
occur first, when individuals are aged approximately 50-59 years. Vertebral fractures occur
more often in the seventh decade of life. Ninety percent of hip fractures occur in persons aged
50 years or older, occurring most often in the eighth decade of life.
Women are at a significantly higher risk for osteoporosis. Half of all postmenopausal
women will have an osteoporosis-related fracture during their lifetime; 25% of these women
will develop a vertebral deformity, and 15% will experience a hip fracture. Risk factors for
hip fracture are similar in different ethnic groups. Men have a higher prevalence of secondary
osteoporosis, with an estimated 45-60% of cases being a consequence of hypogonadism,
alcoholism, or glucocorticoid excess.3 Only 35-40% of osteoporosis diagnosed in men is
considered primary in nature. Overall, osteoporosis has a female-to-male ratio of 4:1.
2.3 Etiology
Osteoporosis has been divided into several classifications according to etiology and
localization in the skeleton. Osteoporosis is initially divided into localized and generalized
categories, and these two main categories are further classified further into primary and
secondary osteoporosis. Postmenopausal osteoporosis (PMO) is primarily due to estrogen
deficiency. Senile osteoporosis is primarily due to an aging skeleton and calcium deficiency.1
Primary osteoporosis
Patients are said to have primary osteoporosis when a secondary cause of osteoporosis
cannot be identified, including juvenile and idiopathic osteoporosis. Idiopathic osteoporosis
can be further subdivided into postmenopausal (type I) and age-associated or senile (type II)
osteoporosis, as described in Table 2, below.
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Usually occurs in children or young
adults of both sexes
Idiopathic osteoporosis
Characterized by a phase of
Postmenopausal osteoporosis
accelerated bone loss, primarily from
(type I osteoporosis)
trabecular bone
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Secondary osteoporosis
Cause Examples
Cystic fibrosis
Ehlers-Danlos syndrome
Gaucher disease
Marfan syndrome
Riley-Day syndrome
Osteogenesis imperfecta
Hemochromatosis
Homocystinuria
Hypophosphatasia
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Idiopathic hypercalciuria
Porphyria
Hypogonadal states
Androgen insensitivity
Hyperprolactinemia
Hypogonadal states
Panhypopituitarism
Premature menopause
Turner syndrome
Klinefelter syndrome
Diabetes mellitus
Acromegaly
Adrenal insufficiency
Estrogen deficiency
Hyperparathyroidism
Hyperthyroidism
Hypogonadism
Pregnancy
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Prolactinoma
Calcium deficiency
Magnesium deficiency
Protein deficiency
Vitamin D deficiency
Bariatric surgery
Gastrectomy
Malabsorption
Malnutrition
Parenteral nutrition
Leukemia
Lymphoma
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Multiple myeloma
Systemic mastocytosis
Thalassemia
Metastatic disease
Anticonvulsants
Antipsychotic drugs
Antiretroviral drugs
Aromatase inhibitors
Furosemide
Medications
Glucocorticoids and corticotropin: prednisone (5
mg/day for 3 mo)
Lithium
Miscellaneous Alcoholism
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Amyloidosis
Depression
Emphysema
HIV/AIDS
Idiopathic scoliosis
Immobility
Multiple sclerosis
Ochronosis
Organ transplantation
Pregnancy/lactation
Sarcoidosis
Weightlessness
Bone is a specialized and mineralised connective tissue that acts as a support to the
body to stand stable. Together with cartilage, they formed the skeletal system, that has three
main functions, which are mechanical function as supportive and the place of insertion of the
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muscles to move, as a protection for the vital organs and bone marrow , and lastly as a
reserve metabolic functions of calcium and phosphate which are used for the maintenance of
homeostasis that is essential to life.
Human bones consist of 80% corticular bones and 20% trabecular bones. Cortical
bones and trabecular bones are made of the same cells and the same matrix elements, but
there are differences in their structure and functions. The main structural difference
quantitatively is 80% to 90% of bone volume 6 kortikular is calcification, while only 15% to
25% of the trabecular volume is calcified (the rest is bone marrow, blood vessels, and
connective tissue). The main function of cortical bone serves as a mechanical (locomotor)
and protector, while trabecular bone as a metabolic function and also plays a role in bone
biomechanics process, especially the spine.5
Remodeling is a process where there is a turn-over from the bones that may allow the
maintenance of the form, quality and quantity of the frameworks. This process is
characterized by the coordinated activation of osteoclasts and osteoblasts, which occurs in
bone multicellular unit (BMUs) in which the activation process of resorption and formation
occur sequentially and continuously.5
Osteoblasts are the cells that responsible for bone formation process, which serves in
the synthesis of bone matrix called osteoid, the protein component of bone tissue. Osteoclasts
are the bone cells responsible for the bone resorption process. Osteoclasts are multinucleated
giant cells and derived from the mononuclear hemopoetic.
In the process of bone formation, osteoblasts begin to work. For differentiation and
maturation, osteoblasts need local growth factors, such as fibroblast grow factor (FGF), bone
morphogenetic proteins (BMPs) and Wnt proteins. Besides that, transcription factors are also
necessary, named as core binding factor-1 or Runx2 or Osterix (Osx).5 These osteoblast
precursors will undergone proliferation and differentition to form preosteoblasts and then
advance into mature osteoblasts. Osteoblasts will be coating bone matrix (osteoid) which
were produced prior to calcification and this calcification process takes about 10 days.
Osteoblast membrane is rich in alkaline phosphatase and contain receptors for parathyroid
hormone and prostaglandin but do not have the receptors for calcitonin. Other than that,
osteoblasts also expressed estrogen receptors, vitamin D3 and a variety of cytokines, such as
colony stimulating factor 1 (CSF1), receptor activator of nuclear factor ligand (RANKL) and
osteoprotegerin (OPG). RANKL plays a role in the maturation of osteoclast precursors as the
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osteoclast precursors have the RANK receptor on their surface. Whereas the effects of
RANKL will be inhibited by OPG.5
Osteocytes are stelat shaped cells that have overhung the cytoplasm (processus) very
long to be related to processes of osteocytes other and also with linning bone cells. In the
matrix, osteocytes located in the cavity, called lacuna, while prosesusnya located in in a
tunnel which is called canaliculi.
After the growth has stalled and the peak bone mass is reached, the bone formation
process will continue on the endosteal surface. The continuous process of bone resorption and
bone formation is called bone remodeling. The bone remodelling is the process of replacing
old bone or damaged, beginning with bone resorption by osteoclasts, followed by bone
formation by osteoblasts. The remodeling process begins with the activation of osteoclasts by
certain cytokines. Osteoclasts will leave cavities called lacunae howship on trabecular bone
or conical cavity (cutting cone) in cortical bone. After resorption is completed, then the
osteoblasts will conduct bone formation in the cavity left by the osteoclasts to form bone
matrix called osteoid, followed by primer mineralization in a short time and then continued
with secondary mineralization in a longer and slower process until the bones become hard.5
In normal young adults, approximately 30% of the total mass of the framework is
updated annually (half life = 20 months). In each unit remodeling, bone resorption by
osteoclasts lasts about three days, with a recovery period of 14 days and 70 days of bone
formation (total = 87 days). Linear bone formation rate was 0.5 mm / day. During this
process, approximately 0:01 mm bone remodeling refurbished in a single unit. Theoretically,
the matrix deposition and calcification balanced, and the balance between the activity of
osteoclasts and osteoblasts, the amount of bone formed in each unit equals the amount of
bone remodeling previously resorbed.5 Thus, the total mass of skeletal remains constant.
Homeostasis of this framework relies on the normal remodeling activity. The level of
activation of new remodeling units, only determine the level of turnover.
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Osteoporosis can be caused both by a failure to build bone and reach peak bone mass
as a young adult and by bone loss later in life. Accelerated bone loss can be affected by
hormonal status, as occurs in perimenopausal women; can impact elderly men and women;
and can be secondary to various disease states and medications.
Aging and loss of gonadal function are the 2 most important factors contributing to
the development of osteoporosis. Studies have shown that bone loss in women accelerates
rapidly in the first years after menopause. The lack of gonadal hormones is thought to up-
regulate osteoclast progenitor cells. Estrogen deficiency leads to increased expression of
RANKL by osteoblasts and decreased release of OPG; increased RANKL results in
recruitment of higher numbers of preosteoclasts as well as increased activity, vigor, and
lifespan of mature osteoclasts.1,6
Estrogen deficiency
Estrogen deficiency not only accelerates bone loss in postmenopausal women but also
plays a role in bone loss in men. Estrogen deficiency can lead to excessive bone resorption
accompanied by inadequate bone formation. Osteoblasts, osteocytes, and osteoclasts all
express estrogen receptors. In addition, estrogen affects bones indirectly through cytokines
and local growth factors. The estrogen-replete state may enhance osteoclast apoptosis via
increased production of transforming growth factor (TGF)beta.
IL-1 has also been shown to be involved in the production of osteoclasts. The
production of IL-1 is increased in bone marrow mononuclear cells from ovariectomized rats.
Administering IL-1 receptor antagonist to these animals prevents the late stages of bone loss
induced by the loss of ovarian function, but it does not prevent the early stages of bone loss.
The increase in the IL-1 in the bone marrow does not appear to be a triggered event but,
rather, a result of removal of the inhibitory effect of sex steroids on IL-6 and other genes
directly regulated by sex steroids.
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T cells also inhibit osteoblast differentiation and activity and cause premature
apoptosis of osteoblasts through cytokines such as IL-7. Finally, estrogen deficiency
sensitizes bone to the effects of parathyroid hormone (PTH).
Aging
After the third decade of life, bone resorption exceeds bone formation and leads to
osteopenia and, in severe situations, osteoporosis. Women lose 30-40% of their cortical bone
and 50% of their trabecular bone over their lifetime, as opposed to men, who lose 15-20% of
their cortical bone and 25-30% of trabecular bone.1
Calcium deficiency
Calcium, vitamin D, and PTH help maintain bone homeostasis. Insufficient dietary
calcium or impaired intestinal absorption of calcium due to aging or disease can lead to
secondary hyperparathyroidism. PTH is secreted in response to low serum calcium levels. It
increases calcium resorption from bone, decreases renal calcium excretion, and increases
renal production of 1,25-dihydroxyvitamin D (1,25[OH] 2 D)an active hormonal form of
vitamin D that optimizes calcium and phosphorus absorption, inhibits PTH synthesis, and
plays a minor role in bone resorption.
Vitamin D deficiency
Osteoporotic fractures
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Fractures occur when bones fall under excess stress. Nearly all hip fractures are
related to falls. The frequency and direction of falls can influence the likelihood and severity
of fractures. The risk of falling may be amplified by neuromuscular impairment due to
vitamin D deficiency with secondary hyperparathyroidism or corticosteroids.
The Wnt family is a highly conserved group of proteins that were initially studied in
relationship with cancer initiation and progression due to their involvement in intercellular
communication. In the past decade, the Wnt signaling cascade has been recognized as a
critical regulator of bone metabolism.
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Wnt signaling plays a key role in the fate of mesenchymal stem cells (MSCs), which
are the progenitor cells of mature bone-forming osteoblasts. MSCs have the capability to
differentiate into adipocytes, chondrocytes, neurons, and muscle cells, as well as into
osteoblasts. Certain Wnt signaling pathways promote the differentiation of MSCs along the
osteoblast lineage. The emerging details about the specific molecules involved in the Wnt
pathway have improved the understanding of bone metabolism and led to the development of
new therapeutic targets for metabolic bone diseases.
Wnt signal activation may progress along one of three pathways, with the canonical
pathway involving -catenin being most relevant to bone metabolism. The canonical Wnt
signaling pathway is initiated by the binding of a Wnt protein to an extracellular co-receptor
complex consisting of Frizzled (Fr) and low density lipoprotein receptorrelated protein5
or 6 (LRP5, LRP6). This activation recruits another protein, Disheveled (Dvl) to the
intracellular segment of the Fz/Dvl co-receptor. This is where -catenin comes into play.6
Several human bone abnormalities have been linked to the Wnt pathway. For
example, a single amino acid substitution in the LRP5 receptor gene has been associated with
high bone mass phenotypes in humans; specifically, the mutant LRP5 receptor had an
impaired interaction with the Wnt signal inhibitor Dickkopf-1 (Dkk-1). Similarly, other
missense mutations of LRP5 have been implicated in other high bone mass diseases such as
Van Buchem disease and osteopetrosis. Conversely, loss-of-function mutations of LRP5 have
resulted in a rare but severe congenital osteoporosis in humans.6
There are also several antagonists to the Wnt pathway. Two of the most well-known
are Dkk-1 and sclerostin (SOST). Dkk-1 is secreted by MSCs and binds to LRP-5 and LRP-
6, thereby competitively inhibiting Wnt signaling. Interestingly, serum levels of Dkk-1
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positively correlate with the extent of lytic bone lesions in patients with multiple myeloma.
Clinical trials of a monoclonal antibody to Dkk-1 are ongoing. Similarly, SOST, a product of
osteocytes, has also been found to antagonize the Wnt signaling pathway by binding to LRP5
and LRP6. A SOST antibody is also undergoing clinical trials for treatment of metabolic bone
disease.
Risk factors for osteoporosis, such as advanced age and reduced bone mineral density
(BMD), have been established by virtue of their direct and strong relationship to the
incidence of fractures; however, many other factors have been considered risk factors based
on their relationship to BMD as a surrogate indicator of osteoporosis.
Female sex
Thin build or small stature (eg, body weight less than 127 lb)
Amenorrhea
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Late menarche
Early menopause
Postmenopausal state
Calcium deficiency
2.7 Diagnosis
Until now, the early detection of osteoporosis is a very difficult thing to do.
Osteoporosis is a silent disease (silent), sometimes it does not give any signs or symptoms
until fracture occurs. Diagnosis of osteoporosis are sometimes only known after the
occurrence of fractures of the spine, hip bones, wrist bones or other fractures in older people,
either men or women. Usually the bone mass is reduced 30-40% and can only be detected by
conventional X-ray examination.
History taking
A thorough history should be obtained to screen for and identify the presence of known
risk factors for osteoporosis and osteoporotic fracture. Specifically, the history should focus
on the following:7
Age (>50 years), sex (female), and race (white or Asian) ; the US Preventive Services
Task Force (USPSTF) recommendations include screening for osteoporosis in women
aged 65 years or older and in younger women with a fracture risk that is the same or
greater than that of a 65-year-old white woman who has no additional risk factors
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Reproductive factors, especially regarding early menopause and estrogen replacement
therapy: postmenopausal women are at high risk, as are women who have undergone
hysterectomy and oophorectomy
Alcohol consumption
Low levels of physical activity: immobility increases the risk; spinal cord injury and
stroke cause physical impairment and are common causes of immobility
Strenuous exercise that results in amenorrhea (such as that which occurs in marathon
runners)
Risk factors for falls in older patients: these include poor balance,orthostatic
hypotension, weakness of the lower extremity muscles and deconditioning, use of
medications with sedative effects, poor vision or hearing, and cognitive impairment
The Fracture Risk Assessment (FRAX) tool, accessible to healthcare providers and
patients, is a validated instrument used to estimate 10-year risks for fractures, including those
for black, Asian, and Hispanic women. A 65-year-old white woman with no other risk factors
has a 9.3% 10-year risk for any osteoporotic fracture. Generally, estimated fracture risks in
nonwhite women are lower than those for white women of the same age.7
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White women between the ages of 50 and 64 years with 10-year fracture risks based on
specific risk factors include the following persons:
A 50-year-old current smoker with a body mass index (BMI) less than 21 kg/m 2,
daily alcohol use, and parental fracture history
A 55-year-old woman with a parental fracture history
A 60-year-old woman with a BMI less than 21 kg/m 2 and daily alcohol use
A 60-year-old current smoker with daily alcohol use
Physical Examination
The examination may elicit pain, or the patient may be pain free. Thoracic kyphosis
may be present secondary to vertebral compression fractures, a dowager hump, and a history
of loss of height. Patients may have an associated scoliosis.2,7
Signs that might indicate existing osteoporosis (eg, kyphosis or dowager hump; point
tenderness over a vertebra or other suspected fracture site)
Signs in older patients that may indicate increased fall risk (eg, difficulty with balance
or gait, orthostatic hypotension, lower-extremity weakness, poor vision or hearing,
cognitive impairment)
Signs of fracture
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lordosis. After each episode of vertebral compression fracture and progressive kyphosis, the
patient's height may decrease by 2-3 cm. Patients with acute vertebral fractures may have
point tenderness over the involved vertebrae. Palpation of the spinous processes often does
not aid the examiner in localizing point tenderness, but percussion may be helpful in acute or
subacute vertebral compression fractures.
Patients with hip fractures may have severe pain with ambulation. A FABER (ie,
flexion in abduction and external rotation) hip joint test may reveal limited ROM with end-
range pain. Patients with hip fractures may show decreased weight-bearing on the fractured
side or an antalgic gait pattern. Patients with pubic and sacral fractures may report marked
pain with ambulation and tenderness to palpation, percussion, or both. Furthermore, patients
with sacral fractures may have pain with physical examination techniques used to assess the
sacroiliac joint, such as the FABER, Gaenslen, or squish test. Fractures in other parts of the
body, including the distal radius and humerus, are typically painful and result in limited range
of motion of the involved joint.1
Balance difficulties
Patients with osteoporosis are known to have decreased balance, possibly secondary
to differences in balance control strategies and sway amplitude. Patients may have difficulty
performing tandem gait and performing single limb stance. Poor balance may be noted
particularly in patients with severe kyphosis resulting from vertebral compression fractures
because their altered center of gravity makes ambulation with a stable base of support
difficult for them. Fractures are the most common and serious complication of osteoporosis.
Patients with osteoporosis are at high risk for recurrent fractures of the hips, vertebrae, ribs,
and wrists.
Radiology examination
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Figure 1: comparison between normal x-ray photo of left foot with x-ray of
osteoporotic left foot
X-Ray Absorptiometry
Several large prospective studies have shown that BMD measurements of the distal
and proximal femur and the vertebral bodies can predict the development of the major types
of osteoporotic fractures. BMD has been shown to be the best indicator of fracture risk.
According to the National Osteoporosis Foundation (NOF), evaluating BMD on a periodic
basis is the best way to monitor bone mass and future fracture risk, although there is
controversy about how frequently to measure this.2
DXA is currently the criterion standard for the evaluation of BMD. Compared with
other screening tools (eg, calcaneal quantitative ultrasonography, the Simple Calculated
Osteoporosis Risk Estimation [SCORE]), DXA has been found to be efficacious and cost-
effective. DXA is not as sensitive as quantitative computed tomography (QCT) scanning for
detecting early trabecular bone loss, but it provides comparable costs, it is done on an
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outpatient basis, and there are no special requirements for performing it. Also, radiation
exposure is kept to a minimum.
DXA is used to calculate BMD at the lumbar spine, hip, and proximal femur (see the
images below). Densitometric spine imaging can be performed at the time of DXA scanning
to detect vertebral fractures. Vertebral fracture assessment (VFA) is not available with all
DXA machines. When available, VFA should be considered when the results may influence
clinical management of the patient. Peripheral DXA is used to measure BMD at the wrist; it
may be most useful in identifying patients at very low fracture risk who require no further
workup.8
Although measurement of BMD at any site can be used to assess overall fracture risk,
measurement at a particular site is the best predictor of fracture risk at that site. Whenever
possible, the same technologist should perform subsequent measurements on the same patient
using the same machine. This method can be used in both adults and children. Factors that
may result in a falsely high BMD determination include spinal fractures, osteophytosis,
scoliosis, and extraspinal (eg, aortic) calcification.
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Bone density data from a DXA are reported as T-scores and Z-scores. The T-score is
the value compared to that of control subjects who are at their peak BMD, whereas the Z-
score reflects a value compared to that of patients matched for age and sex.8
The 2014 NOF guidelines recommend BMD measurement in the following patients:
Women age 65 years and older and men age 70 years and older, regardless of clinical
risk factors
Men age 50-69 years with clinical risk factors for fracture
Adults who have a condition associated with low bone mass or bone loss (eg,
rheumatoid arthritis)
Adults who take a medication associated with low bone mass or bone loss (eg,
glucocorticoids, 5 mg of prednisone daily for 3 mo)
Differential diagnosis
Some diseases can cause a decrease in bone mass density and fractures. Therefore, if
there is a patient with a decrease in bone mass density or fractures, the underlying disease
need to be found first. Some diseases that may cause a decrease in bone mass density can be
made as a differential diagnosis. History and physical examination based on the clinical
symptoms is still needed to be done to make the diagnosis of osteoporosis, including the
underlying disease of osteoporosis (secondary osteoporosis). Investigations, such as
laboratories are very helpful in getting rid of the differential diagnosis of disease. As for some
illness or chronic condition that often leads to osteoporosis are as follows:
1. Multiple myeloma
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classic triad (plasma cells, typically> 10% + M protein + lytic bone lesions). 1,2 Laboratory
tests for the diagnosis of MM is albumin-globulin, serum protein electrophoresis, Bence-
Jones protein urine, hypercalcemia, increased in ureum-creatinine and abnormal plasma cells
seen in blood films in 15% of patients.
2. Hyperparathyroidism
The main effects of parathyroid hormone are to increase the concentration of plasma
calcium by increasing the release of calcium and phosphate from bone matrix, increasing
calcium reabsorption by the kidney, and increasing renal production of 1,25-
dihydroxyvitamin D-3 (calcitriol), which increases intestinal absorption of calcium. 5,7
Hyperparathyroidism come in two forms which are primary and secondary. Primary
hyperparathyroidism is due to excessive functions of the parathyroid glands, usually the
adenoma. Primary hyperparathyroidism will result in high concentration of parathyroid
hormone serum, and high calcium serum. Secondary hyperparathyroidism is the excessive
production of parathyroid hormone due to stimulation by abnormal production. Secondary
hyperparathyroidism is a compensatory hyperplasia of all four glands which aims to correct a
decrease in serum calcium levels. Most patients with hyperparathyroidism are asymptomatic.
Its manifestations are especially on the kidneys and bones. Abnormalities in the kidneys that
can be found are recurrent nephrolithiasis, urinary tract obstruction, infection, and renal
function failure. Laboratory tests may show increased serum levels of parathyroid hormone,
high calcium serum, low phosphate, high alkali phosphatase, high urinary calcium and
phosphate, 25 hydroxyvitamin D is low, kidney function tests. On X-rays, the bones become
thin, decalcification occurs, and bone cystic may present.
2.8 Therapy
Pharmacological
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Bisphosphonates
Bisphosphonates taken orally are absorbed in the small intestine and its absorption is
very poor. The absorption of this drug can also be hampered if taken together with calcium,
other divalent cations, and various other drinks except water. Ideally taken in the morning on
an empty stomach. After that the patient is not allowed to eat anything and lying down for at
least 30 minutes. Approximately 20-50% of the bisphosphonate absorbed, will be attached to
the bone surface after 12-24 hours.1 After binding to the bone and act on the osteoclasts,
bisphosphonate will remain in the bone for months or even years, but no longer active.
Bisphosphonates that are not attached to the bone, will not undergone metabolism in the body
and will be excreted in the intact form through the kidneys, so be careful of administration of
this drug to the patients with renal failure. The side effects of bisphosphonate is reflux
esophagitis, osteonecrosis of the jaw, hypocalcemia and atrial fibrillation. Therefore, patients
who obtained bisphosphonates, their calcium intake should be watched too.
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of 40 mg / day for 6 months. Alendronate is not recommended in patients with renal
impairment (creatinine clearance <35 ml / min).
3. Ibandronate, is also a third generation bisphosphonate. It can be taken orally with a dose of
2.5 mg / day or 150 mg once a month. Ibandronate can also be administered intravenously at
a dose of 3 mg, once in 3 months. Contra indications for ibandronate administration is
hypocalcemia.3
Raloxifene has been shown to prevent bone loss, and data in females with
osteoporosis have demonstrated that this agent causes a 35% reduction in the risk of vertebral
fractures. It has also been shown to reduce the prevalence of invasive breast cancer.
Raloxifene may be most useful in younger postmenopausal women without severe
osteoporosis. It has been shown to increase the incidence of deep vein thrombosis, stroke, and
hot flashes. In 601 postmenopausal women who had daily therapy with raloxifene, BMD was
increased, serum concentrations of total low-density lipoprotein cholesterol were lowered,
and the endometrium was not stimulated.
Parathyroid hormones
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treatment has failed to increase bone mass. It is indicated in men with idiopathic or
hypogonadal osteoporosis who are at high risk of fracture, who have been intolerant of
previous osteoporosis therapy, or in whom osteoporosis therapy has failed. Teriparatide is
also approved for the treatment of patients with glucocorticoid-induced osteoporosis. Before
treatment with teriparatide, levels of serum calcium, PTH, and 25(OH)D need to be
monitored.1,7
Indications for PTH in men and women are a bone density decline while on
bisphosphonate therapy, bone density stabilization while on extremely low-level
bisphosphonate therapy, a fracture occurring while on bisphosphonate therapy, or a very low
initial bone turnover rate for which an anabolic effect is clearly warranted. Teriparatide
should be considered in younger and older postmenopausal women with severe osteoporosis.
Calcitonin
Results from a single controlled clinical trial indicate that calcitonin may decrease
osteoporotic vertebral fractures by approximately 30%. In the first 2 years, calcitonin has
been found to increase spinal bone mineral density (BMD) by approximately 2%. Calcitonin
also has an analgesic property that makes it ideally suited for the treatment of acute vertebral
fractures.
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Calcitonin is an option for patients who are not candidates for other available
osteoporosis treatments. Common side effects of nasally administered calcitonin include
nasal discomfort, rhinitis, irritation of nasal mucosa, and occasional epistaxis. Nausea, local
inflammatory reactions at the injection site, sweating, and flushing are side effects noted with
parenteral use.
Denosumab
Because it is a newer drug and there are no long-term safety data, denosumab is
usually reserved for patients who are intolerant of or unresponsive to oral and/or intravenous
bisphosphonates. Denosumab should not be given to patients with low blood calcium until it
is corrected.
Commonly used calcium supplements include calcium carbonate and calcium citrate.
Calcium carbonate is generally less expensive and is recommended as a first choice option.
Calcium carbonate has better absorption with food, as opposed to calcium citrate, which is
better absorbed in the fasting state. Also, fewer tablets are needed with calcium carbonate
than with calcium citrate.
Non-pharmacological
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Physical therapy focuses on improving a patient's strength, flexibility, posture, and
balance to prevent falls and maximize physical function. Postural retraining is key in this
population. Spinal bone mineral density (BMD) is directly correlated with the strength of the
back extensors; therefore, maintaining and strengthening the back extensors should be
emphasized. In studies by Sinaki and colleagues, strengthening the back extensor muscles
reduced kyphosis and decreased the risk of sustaining vertebral compression fractures.7
Surgery
1. Advanced age patients with osteoporosis related fracture, if required surgery, should be
done immediately. This is to avoid prolonged immobilization and further complications of
fracture.
2. The purpose of surgical treatment is to obtain a stable fixation until the patients
mobilisation can be achieved as early as possible.
3. Calcium intake should still be considered for patients who had undergone surgery, until the
callus mineralization turned perfect.
4. Although the required surgery had been done, medical management of osteoporosis with
bisphosphonates or raloxifene or hormone replacement therapy, or calcitonin should still be
given.
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CHAPTER III
CONCLUSION
The cells that responsible for bone formation called osteoblasts, while osteoclasts are
responsible for bone resorption. In osteoporosis bone turnover abnormalities will occur in
which the process of bone resorption are more than the process of bone formation. This
situation resulted in a decrease in bone mass leading to osteoporosis. Densitometry
examination by using Dual Energy X-ray Absorptiometry is the gold standard for diagnosis
of osteoporosis.
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REFERENCES
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