Bone Structure and Function
• The physical and chemical properties of
bone relate to its three main functions:
•  provision of support
•  protection
•  calcium homeostasis
Macroscopically, there are two types of
bone:
•  dense cortical bone
•  spongy cancellous bone
Bone Structure and Function
•  Cortical bone is located in the diaphyses of long
bones and on the surfaces of flat bones. There is
also a thin cortical shell at the epiphyses and
metaphyses of long bones.
•
Trabecular bone is limited to the epiphyseal
and metaphyseal regions of long bones and is
present within the cortical coverings in the
smaller flat and short bones.
Osso
trabecolare
Osso
corticale
Osso
trabecolare
Bone Structure and Function
The difference between cortical bone and
trabecular bone is both structural and
functional.
The structural differences are essentially
quantitative: 80-90% of the volume of compact
bone is calcified vs. 15-25% in trabecular bone
(the remaining volume is occupied by the marrow)
Cortical bone fulfils mainly (but not exclusively)
a mechanical and protective function and the
trabecular bone a metabolic function.
Bone Structure and Function
Bone
turnover
is
mediated
by
coupling of the bone-forming cellular
activity of osteoblasts and the boneresorbing osteoclasts.
Bone Structure and Function
The osteoblast is the
bone cell responsible for
the production of the
matrix constituents
(collagen and ground
substance). It also plays
an important part in the
calcification process.
It originates from a local
mesenchymal stem cell
(bone marrow stromal
stem cell or connective
tissue mesenchymal cell).
Bone Structure and Function
The osteoclast is the bone
cell responsible for bone
resorption.
It is a giant multinucleated
cell (4-20 nuclei)
Its progenitor is related to
the monocyte-macrophage
family.
Bone Structure and Function
Where the bone is in contact with the
soft tissues is an external surface
(periosteal) and where the bone is in
contact with the bone marrow an
internal surface (endosteal).
These
surfaces
are
lined
with
osteogenic cells organized in layers
termed the periosteum and endosteum,
respectively.
The Remodeling Cycle on a Trabecula
The activity of bone cells along the surfaces of bone, mainly
the endosteal surface, results in bone remodeling. This is
the process by which bone grows and is turned over.
N Engl J Med 2006;354;21
Osteoporosis
The most common type of metabolic bone disease.
Parallel reduction in bone mineral and bone matrix.
The bone is decreased in amount but is of normal composition.
The strength of bone is reduced and the risk of fracture is
increased.
Normal bone
Osteoporosis
Osteoporosis
Primary osteoporosis:
reduced bone mass and fractures in
postmenopausal women (type I, or
‘postmenopausal’ osteoporosis) or in older
men and women due to age-related
factors (type II osteoporosis).
Secondary osteoporosis:
bone loss resulting from specific clinical
disorders, such as thyrotoxicosis or
hyperadrenocorticism.
Tipi di osteoporosi primaria
Tipo I
Postmenopausale
Tipo II
Senile
Età (anni)
50-70
>70
Osso interessato
Principalmente
trabecolare
Trabecolare e
corticale
Sedi di frattura
Vertebre
Radio (Colles)
Femore
prossimale
Causa principale
Menopausa
Invecchiamento
Osteoporosis
  Osteoporosis affects over 20 million Americans
and leads to approximately 1.5 million fractures in
the United States each year.
  During the course of their lifetime, women lose
about 50% of their trabecular bone and 30% of
their cortical bone.
  About 40% of all postmenopausal white women
eventually sustain osteoporotic fractures.
  By extreme old age, one third of all women and
one sixth of all men will have a hip fracture.
Osteoporosis
At any age, women experience twice as
many osteoporosis-related fractures as
men,
reflecting
gender-related
differences in skeletal properties as well
as the almost universal loss of bone at
menopause.
However, osteoporotic fractures in
older men should not be considered
trivial.
Osteoporosis
Osteoporotic fractures are a
major public health problem for
older women and men in Western
society.
Half the men and women over age
55 have low bone mass or
osteoporosis, placing them at
increased risk of fracture.
Incidence of
osteoporotic
fractures in
men
Incidence of
osteoporotic
fractures in
women
Osteoporosis
  One white woman in six suffers a hip
fracture; mortality after hip fracture ranges
from 12–20% in the first year.
  One-third of hip fractures occur in men and
have been associated with an even higher
mortality rate than in women.
  Billions of dollars are spent annually for acute
hospital care of hip fracture alone.
Osteoporosis
The
consequences
of
vertebral
deformity are also significant and include
chronic pain, inability to conduct daily
activities, depression, and high risk of
further vertebral fractures.
Peak bone mass
The amount of bone mineral present at
any time in adult life represents that
which has been gained at skeletal
maturity (peak bone mass) minus that
which has been subsequently lost. Bone
acquisition is completed in the late
teenage years and early twenties in girls
and by the second decade in boys.
At any point in time, bone density in adults depends on
both the peak bone density achieved during development
and the subsequent bone loss.
Thus, osteopenia can result from deficient pubertal
bone accretion, accelerated adult bone loss, or both.
Factors that may affect
peak bone mass
Gender
Race
Genetic factors
Gonadal steroids
Growth hormone
Timing of puberty
Calcium intake
Exercise
Other disorders associated with
reduced peak bone mass
Anorexia nervosa
Ankylosing spondylitis
Childhood immobilization (‘therapeutic bed rest’)
Cystic fibrosis
Delayed puberty
Exercise-associated amenorrhea
Galactosemia
Intestinal or renal disease
Marfan's syndrome
Osteogenesis imperfecta
Serum estradiol concentrations risk of subsequent hip or
vertebral fracture in postmenopausal women
Regulation of osteoclast development
RANKL: Receptor Activator of Nuclear factor-κB Ligand
OPG: osteoprotegerin (decoy receptor)
Causes of osteoporosis according to
probable mechanism
High turnover (increased bone resorption greater
than increased bone formation)
•  Estrogen deficiency - primarily in postmenopausal
women
•  Hyperparathyroidism
•  Hyperthyroidism
•  Hypogonadism in young women and in men
•  Cyclosporine (?)
•  Heparin
Causes of osteoporosis according
to probable mechanism
Low turnover (decreased bone formation more
pronounced than decreased bone resorption)
• Liver disease – primarily primary biliary cirrhosis
•  Heparin
•  Age above 50 years
Increased bone resorption and decreased bone
formation
•  Glucocorticoids
Diseases associated with secondary osteoporosis
Endocrine diseases
Hypogonadism
Hyperparathyroidism
Hyperthyroidism
Hypercortisolism
Hyperprolactinemia
Diabetes mellitus, type I
Gastrointestinal diseases
Inflammatory bowel disease
Malabsorption syndromes
Celiac disease
Chronic liver disease
Gastric bypass operations
Diseases associated with secondary osteoporosis
Other chronic diseases
Chronic rheumatic disorders
Rheumatoid arthritis
Ankylosing spondylitis
Chronic obstructive pulmonary disease
Renal disorders
Renal tubular acidosis
Idiopathic hypercalciuria
Malignancy
Multiple myeloma
Metastatic disease
Infiltrative disorders
Systemic mastocytosis
Hereditary disorders of connective tissue
Osteogenesis imperfecta
Diseases associated with secondary
osteoporosis
Organ transplantation
Dietary disorders
Vitamin D deficiency and insufficiency
Calcium deficiency
Excessive alcohol intake
Anorexia nervosa
Total parenteral nutrition
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Frattura di Colles
Frattura del collo del femore
Mineralometria ossea computerizzata
Mineralometria ossea computerizzata
DEXA: Dual Energy X-ray Absorptiometry
The T score is the number of standard deviations
by which the patient's bone density differs from
the peak bone density of individuals of the same
gender and ethnicity.
The Z score is the number of standard deviations
by which the patient's bone density differs from
bone density of age-matched individuals of the
same gender and ethnicity.
Diagnostic categories for osteopenia and
osteoporosis based upon bone mass measurements
Normal
A value for bone mineral density (BMD) or bone mineral
content (BMC) within one standard deviation of the young
adult reference mean.
Low bone mass (osteopenia)
A value for BMD or BMC more than one and less than 2.5
standard deviations below the young adult reference mean.
Osteoporosis
A value for BMD or BMC more than 2.5 standard
deviations below the young adult reference meanSevere
(established) osteoporosisA value for BMD or BMC more
than 2.5 standard deviations below the young adult
reference mean in the presence of one or more fragility
fractures.
Biochemical Markers of Bone Metabolism in
Clinical Use
Bone formation
Serum bone-specific alkaline phosphatase
Serum osteocalcin
Serum propeptide of type I procollagen
Bone resorption
Urine and serum cross-linked N-telopeptide
Urine and serum cross-linked C-telopeptide
Urine total free deoxypyridinoline
Urine hydroxyproline
Serum tartrate-resistant acid phosphatase
Serum bone sialoprotein
Urine hydroxylysine glycosides
Risk Factors for Osteoporosis
Fracture
Nonmodifiable •
•
•
•
•
•
Personal history of fracture as an adult History of fracture in first-degree relative Female sex Advanced age Caucasian race Dementia
Risk Factors for Osteoporosis Fracture
Potentially modifiable
•  Current cigarette smoking •  Low body weight [<58 kg)
•  Estrogen deficiency •  Early menopause (<45 years) or bilateral ovariectomy •  Prolonged premenstrual amenorrhea (>1 year) •  Low calcium intake •  Alcoholism •  Impaired eyesight despite adequate correction •  Recurrent falls •  Inadequate physical activity •  Poor health/frailty
•  Osteoporosis means increased bony fragility
and is clinically defined as reduced bone mass
(osteopenia) to an extent sufficient to result
in fracture with minimal trauma.
•  Osteoporosis is the most common disease
that affects bone. Fractures are not usually
manifest until patients have bone mass
30-40% below normal values.
•  Osteoporosis
is a multifactorial disease and
not solely the inevitable consequence of aging.
•  Osteoporotic fractures are most frequent in the
spine, the hip and wrist but virtually any bone can
be affected.
•
Osteoporosis is more common in women than in
men, but is an increasing public health problem in
both sexes in aging populations.
•  One third of women over the age of 65 will have
vertebral fractures, and the life-time risk of hip
fracture in Caucasian women is 16% and in men 5%.
•
Osteoporosis is associated with high morbidity
and, in the case of hip fracture, increased
mortality.
•  Osteoporosis is of considerable socioeconomic
importance because of the high prevalence of
fracture and the enormous costs in health care
required to deal with the consequences of these
fractures.
•  Osteoporosis
can be prevented in patients at
risk by maximizing peak bone mass and
prevention of major bone loss. Therapies are
also available for restoration of bone mass in
those patients with existing bone loss.
Osteomalacia
Defective skeletal
mineralization in adults
Osteomalacia: symptoms and signs
•  Vitamin D deficiency
•  Dietary calcium deficiency
•  Phosphate deficiency
•  Oncogenic osteomalacia
•  Fibrogenesis imperfecta
Osteomalacia: essentials
of diagnosis
  Bone pain and tenderness
  Decreased bone density
  Increased alkaline phosphatase
  Decreased 25(OH)D3
Osteomalacia: symptoms and signs
  Initially asymptomatic
  Eventually, bone pain, simulating fibromyalgia
  Painful proximal muscle weakness (especially
pelvic girdle) due to calcium deficiency
  Fractures with little or no trauma
Looser-Milkman pseudofractures
The primary
source of
vitamin D in
humans is
photoactivation.
Osteomalacia: laboratory tests
  Alkaline phosphatase (age-adjusted) may be elevated
  25(OH)D3 typically low < 20 ng/mL (< 50 nmol/L)
  Calcium or phosphate (age-adjusted) may be low
  Phosphate low in 47%
  Parathyroid hormone may be increased due to
secondary hyperparathyroidism
  Urinary calcium may be low
  1,25(OH)2D3 may be low
  Screen for hypophosphatasia