Osteoporosis
Osteoporosis is a systematic skeletal disorder characterized by low bone mass,
microarchitectural deterioration of bone tissue and susceptibility to fracture. It can be
divided into primary and secondary. Modeling occurs through the activation of cells followed
by either formation or resorption. Remodeling, on the other hand, is defined by the
sequential processes on the same bone surface of activation-resorption-formation (the A-R-F
sequence) describing the process by which resorption of old bone is continuously replaced
by the formation of new bone. The function of remodeling is bone maintenance and repair
of microdamage, not increase in bone mass. Growth, modeling and remodeling are present
concurrently in all growing children. When skeletal maturity is reached, growth naturally
stops and modeling slows down or stops.
Osteoporotic fractures represent a major public health problem because they
increase morbidity and certain fractures (ex. hip and vertebral) are associated with increased
mortality. In 1994 osteoporosis was defined as a state in which BMD in women falls more
than 2.5 SD below the young adult mean. This definition, however, takes into account only
deterioration in bone mineralization and does not consider any of the microarchitectural
changes that may weaken bone independently of any effect on BMD. More recently, there
has been a move toward assessing an individual’s absolute risk for osteoporotic fracture, an
example of which is the FRAX tool.
Primary osteoporosis accounts for >95% of osteoporosis in women and 70-80% in
men. Secondary osteoporosis accounts for <5% of cases of osteoporosis in women but up to
30% in men.
Diagnosis
For postmenopausal women and men ≥50yrs
i) T-score ≤-2.5
ii) spine or hip fragility fracture regardless of BMD
iii) wrist fracture + low BMD
For premenopausal women and men <50yrs: Z-score ≤-2.0 + fragility fracture or a major
risk factor for osteoporosis (hypogonadism, GC, hyperparathyroidism)
Risk factors
•Major
-age, sex
-a previous fracture and a maternal history of fracture (2x hip fracture risk)
-low body weight and weight loss (ex. anorexia nervosa)
-GC use
-drugs (aromatase inhibitors, anti-androgens, anticonvulsants, thiazolidinediones, […])
-alcohol (>2 drinks/d), smoking, caffeine intake
-late age at menarche, early age at menopause
•Additional risk factors
-physical inactivity
-low dietary Ca+2 intake
-renal, hepatic disorders
-endocrine disorders
-rheumatologic disease
•Protective factors: greater height, weight and muscle strength, increased dietary Ca +2,
greater physical activity, later age at menopause and postmenopausal estrogen use.
,Risk stratification
High risk
-previous fragility fracture
-T ≤-2,5
-FRAX score (vertebral ≥20%, hip ≥3%) (when osteopenic)
Very high risk (no consensus on the definition)
-T-score ≤-3.0 without fragility fracture
-T-score ≤-2.5 + 1 fragility fracture
-Multiple vertebral fragility fractures (≥2)
BDM / DEXA
Trabecular/spongy bone = more metabolically active, rapidly remodeling bone (ex. spine,
femoral head, pelvis, ribs). Functions for mineral homeostasis and shock absorption.
Cortical bone = dense compact bone in the diaphysis of long bones (ex. distal 1/3 of radius)
and the cortex of all bones.
loss of cortical bone is characteristic of hyperparathyroidism; in this case DEXA at
distal 1/3 radius (not the ultradistal part in contact with the wrist, that’s mostly trabecular).
•T-score: compares a person’s BMD to the average BMD of a healthy young adult (≈30yrs).
•Z-score: compares a person’s BMD to the average BMD of people of the same age, sex and
ethnicity.
Peak bone mass is achieved in men and women by the mid-20s. It then plateaus for around
10 years before falling at a rate of 0.3-0.5%/year. At menopause the rate of bone loss in
women accelerates to around 3-5%/year for 5-7 years before returning to the previous rate
of decline. Risk for osteoporotic fracture increases continuously as BMD declines, with a 1.5-
3x increase in risk for fracture for each SD fall in BMD. Low BMD can reflect a diagnosis other
than osteoporosis, like metabolic bone disorders and other. DEXA cannot differentiate
between these different reasons for low BMD.
The WHO recommends that the international standard for diagnosis of osteoporosis
be made using the T-score measured by DXA at the femoral neck. However, the BHOF and
the ISCD suggest DXA using the lowest mean T-score of the lumbar spine (ideally L1-L4, but
exclude any vertebra with more than 1SD difference to its neighboring vertebra), total
proximal femur or femoral neck. The WHO densitometric diagnostic criteria can be applied
to DEXA total hip, femoral neck, lumbar spine or distal 1/3 radius (this is reserved for
patients in whom spine or hip BMD is technically invalid, patients too heavy for DXA or
patients with hyperparathyroidism). Some data say that total hip is a better indicator than
femoral head for fracture risk calculation.
Since hip fracture is often associated with significant morbidity and mortality
compared with other fractures, DXA of the hip is generally regarded as the best site for
diagnosis of osteoporosis. In early menopause, however, there is greater BMD loss at the
spine than the hip and therefore, lumbar spine measurement may be helpful in this setting.
For monitoring, since the spine responds quicker, spine DXA is preferred.
Comparison should be done using BMD, not T-score, preferably by the same
instrument. Note that BMD is expressed in surface units (g/cm 2) as DEXA is a 2-D mode.
Bone loss needs to exceed 30-40% before being visible in X-ray!
DEXA must be performed 48h after IVC or 1wk after p.os. gastrographin.
ISCD (2019) recommended BMD testing in the following:
, -All women ≥65yrs and men ≥70yrs regardless of risk factors.
-Postmenopausal women and men aged 50-70yrs with risk factors.
-Women in the menopausal transition with one of risk factor (low body weight, prior low-
trauma fracture or high-risk medications)
-Adults with fragility fractures
-Adults with a condition or taking a medication associated with low bone mass or bone loss.
-Anyone being considered for pharmacologic therapy for osteoporosis.
-Anyone being treated for osteoporosis to monitor response to therapy.
-Anyone not receiving therapy when evidence of bone loss would lead to treatment.
-Postmenopausal women discontinuing estrogen.
The relationship between BMD and osteoporosis can be compared with that between blood
pressure and stroke. Although hypertension is a risk factor for stroke, stroke can occur in
individuals with normal blood pressure.
Overestimation of BMD Underestimation of BMD
-Degenerative spinal changes -Laminectomy (πεταλεκτομή)
-Vertebral fracture -Lytic metastases
-Aortic calcification
-Overlying metals and barium contrast
-Sclerotic metastases
It is important to note that BMD is only one component of bone strength and that 50% of
osteoporotic fractures occur T-score ≥-2.5 (as in GIOP).
*The trabecular bone score (TBS) is a surrogate measure of bone microarchitecture.
It is an independent risk factor from BMD and FRAX scores may be adjusted for TBS, if
available.
Fractures
Major osteoporotic fracture = non-traumatic (fragility) or pathological fractures of the spine,
hip, wrist, shoulder.
Osteoporosis can be diagnosed on the basis of a fragility fracture (=occurring with a
fall from standing height, standing or walking, or even lower levels such as slipping out of a
chair). Hip fracture is the most devastating consequence of osteoporosis. Only 25% of
vertebral fractures result from falls and most are precipitated by routine daily activities such
as bending or lifting light objects. Only 35% of all vertebral deformities noted on Rx come to
medical attention, as 1/3 of all vertebral fractures are painful, but 2/3 are asymptomatic.
Frequency of fractures: vertebral >hip > wrist. Most serious fractures (more
consequences and mortality): hip > vertebral. Radiographically evident vertebral fractures
are the most common fractures in men and women. In general, the presence of previous
vertebral deformities has been shown to increase the risk for subsequent vertebral
deformities by 7-10x. This is comparable to the increase in risk for a second hip fracture
observed in those who have already sustained a first hip fracture. Patients with a prevalent
(preexisting) vertebral fracture have 4x greater risk for further vertebral fractures than do
patients without a prevalent fracture, as well as 2x the risk for hip and other non-vertebral
fractures. After experiencing an initial vertebral fracture, 20% of postmenopausal women
with osteoporosis sustain an additional vertebral fracture within 1 year. A woman’s lifetime
risk for fracture is 40% and for hip fracture, 16%.
Baseline vertebral fracture assessment may be indicated if:
T-score <-1.0 + one or more of the following:
Osteoporosis is a systematic skeletal disorder characterized by low bone mass,
microarchitectural deterioration of bone tissue and susceptibility to fracture. It can be
divided into primary and secondary. Modeling occurs through the activation of cells followed
by either formation or resorption. Remodeling, on the other hand, is defined by the
sequential processes on the same bone surface of activation-resorption-formation (the A-R-F
sequence) describing the process by which resorption of old bone is continuously replaced
by the formation of new bone. The function of remodeling is bone maintenance and repair
of microdamage, not increase in bone mass. Growth, modeling and remodeling are present
concurrently in all growing children. When skeletal maturity is reached, growth naturally
stops and modeling slows down or stops.
Osteoporotic fractures represent a major public health problem because they
increase morbidity and certain fractures (ex. hip and vertebral) are associated with increased
mortality. In 1994 osteoporosis was defined as a state in which BMD in women falls more
than 2.5 SD below the young adult mean. This definition, however, takes into account only
deterioration in bone mineralization and does not consider any of the microarchitectural
changes that may weaken bone independently of any effect on BMD. More recently, there
has been a move toward assessing an individual’s absolute risk for osteoporotic fracture, an
example of which is the FRAX tool.
Primary osteoporosis accounts for >95% of osteoporosis in women and 70-80% in
men. Secondary osteoporosis accounts for <5% of cases of osteoporosis in women but up to
30% in men.
Diagnosis
For postmenopausal women and men ≥50yrs
i) T-score ≤-2.5
ii) spine or hip fragility fracture regardless of BMD
iii) wrist fracture + low BMD
For premenopausal women and men <50yrs: Z-score ≤-2.0 + fragility fracture or a major
risk factor for osteoporosis (hypogonadism, GC, hyperparathyroidism)
Risk factors
•Major
-age, sex
-a previous fracture and a maternal history of fracture (2x hip fracture risk)
-low body weight and weight loss (ex. anorexia nervosa)
-GC use
-drugs (aromatase inhibitors, anti-androgens, anticonvulsants, thiazolidinediones, […])
-alcohol (>2 drinks/d), smoking, caffeine intake
-late age at menarche, early age at menopause
•Additional risk factors
-physical inactivity
-low dietary Ca+2 intake
-renal, hepatic disorders
-endocrine disorders
-rheumatologic disease
•Protective factors: greater height, weight and muscle strength, increased dietary Ca +2,
greater physical activity, later age at menopause and postmenopausal estrogen use.
,Risk stratification
High risk
-previous fragility fracture
-T ≤-2,5
-FRAX score (vertebral ≥20%, hip ≥3%) (when osteopenic)
Very high risk (no consensus on the definition)
-T-score ≤-3.0 without fragility fracture
-T-score ≤-2.5 + 1 fragility fracture
-Multiple vertebral fragility fractures (≥2)
BDM / DEXA
Trabecular/spongy bone = more metabolically active, rapidly remodeling bone (ex. spine,
femoral head, pelvis, ribs). Functions for mineral homeostasis and shock absorption.
Cortical bone = dense compact bone in the diaphysis of long bones (ex. distal 1/3 of radius)
and the cortex of all bones.
loss of cortical bone is characteristic of hyperparathyroidism; in this case DEXA at
distal 1/3 radius (not the ultradistal part in contact with the wrist, that’s mostly trabecular).
•T-score: compares a person’s BMD to the average BMD of a healthy young adult (≈30yrs).
•Z-score: compares a person’s BMD to the average BMD of people of the same age, sex and
ethnicity.
Peak bone mass is achieved in men and women by the mid-20s. It then plateaus for around
10 years before falling at a rate of 0.3-0.5%/year. At menopause the rate of bone loss in
women accelerates to around 3-5%/year for 5-7 years before returning to the previous rate
of decline. Risk for osteoporotic fracture increases continuously as BMD declines, with a 1.5-
3x increase in risk for fracture for each SD fall in BMD. Low BMD can reflect a diagnosis other
than osteoporosis, like metabolic bone disorders and other. DEXA cannot differentiate
between these different reasons for low BMD.
The WHO recommends that the international standard for diagnosis of osteoporosis
be made using the T-score measured by DXA at the femoral neck. However, the BHOF and
the ISCD suggest DXA using the lowest mean T-score of the lumbar spine (ideally L1-L4, but
exclude any vertebra with more than 1SD difference to its neighboring vertebra), total
proximal femur or femoral neck. The WHO densitometric diagnostic criteria can be applied
to DEXA total hip, femoral neck, lumbar spine or distal 1/3 radius (this is reserved for
patients in whom spine or hip BMD is technically invalid, patients too heavy for DXA or
patients with hyperparathyroidism). Some data say that total hip is a better indicator than
femoral head for fracture risk calculation.
Since hip fracture is often associated with significant morbidity and mortality
compared with other fractures, DXA of the hip is generally regarded as the best site for
diagnosis of osteoporosis. In early menopause, however, there is greater BMD loss at the
spine than the hip and therefore, lumbar spine measurement may be helpful in this setting.
For monitoring, since the spine responds quicker, spine DXA is preferred.
Comparison should be done using BMD, not T-score, preferably by the same
instrument. Note that BMD is expressed in surface units (g/cm 2) as DEXA is a 2-D mode.
Bone loss needs to exceed 30-40% before being visible in X-ray!
DEXA must be performed 48h after IVC or 1wk after p.os. gastrographin.
ISCD (2019) recommended BMD testing in the following:
, -All women ≥65yrs and men ≥70yrs regardless of risk factors.
-Postmenopausal women and men aged 50-70yrs with risk factors.
-Women in the menopausal transition with one of risk factor (low body weight, prior low-
trauma fracture or high-risk medications)
-Adults with fragility fractures
-Adults with a condition or taking a medication associated with low bone mass or bone loss.
-Anyone being considered for pharmacologic therapy for osteoporosis.
-Anyone being treated for osteoporosis to monitor response to therapy.
-Anyone not receiving therapy when evidence of bone loss would lead to treatment.
-Postmenopausal women discontinuing estrogen.
The relationship between BMD and osteoporosis can be compared with that between blood
pressure and stroke. Although hypertension is a risk factor for stroke, stroke can occur in
individuals with normal blood pressure.
Overestimation of BMD Underestimation of BMD
-Degenerative spinal changes -Laminectomy (πεταλεκτομή)
-Vertebral fracture -Lytic metastases
-Aortic calcification
-Overlying metals and barium contrast
-Sclerotic metastases
It is important to note that BMD is only one component of bone strength and that 50% of
osteoporotic fractures occur T-score ≥-2.5 (as in GIOP).
*The trabecular bone score (TBS) is a surrogate measure of bone microarchitecture.
It is an independent risk factor from BMD and FRAX scores may be adjusted for TBS, if
available.
Fractures
Major osteoporotic fracture = non-traumatic (fragility) or pathological fractures of the spine,
hip, wrist, shoulder.
Osteoporosis can be diagnosed on the basis of a fragility fracture (=occurring with a
fall from standing height, standing or walking, or even lower levels such as slipping out of a
chair). Hip fracture is the most devastating consequence of osteoporosis. Only 25% of
vertebral fractures result from falls and most are precipitated by routine daily activities such
as bending or lifting light objects. Only 35% of all vertebral deformities noted on Rx come to
medical attention, as 1/3 of all vertebral fractures are painful, but 2/3 are asymptomatic.
Frequency of fractures: vertebral >hip > wrist. Most serious fractures (more
consequences and mortality): hip > vertebral. Radiographically evident vertebral fractures
are the most common fractures in men and women. In general, the presence of previous
vertebral deformities has been shown to increase the risk for subsequent vertebral
deformities by 7-10x. This is comparable to the increase in risk for a second hip fracture
observed in those who have already sustained a first hip fracture. Patients with a prevalent
(preexisting) vertebral fracture have 4x greater risk for further vertebral fractures than do
patients without a prevalent fracture, as well as 2x the risk for hip and other non-vertebral
fractures. After experiencing an initial vertebral fracture, 20% of postmenopausal women
with osteoporosis sustain an additional vertebral fracture within 1 year. A woman’s lifetime
risk for fracture is 40% and for hip fracture, 16%.
Baseline vertebral fracture assessment may be indicated if:
T-score <-1.0 + one or more of the following:
