Jonathan D. Adachi, MD FRCP(C) Professor,
Department of Medicine St. Joseph's Hospital - McMaster University Hamilton, Ontario
Charlton Ave. East, Suite 501, Hamilton, Ontario L8N IY2
Rheumatology with an interest in Metabolic Bone Disease
Telephone: Area Code 905 529 1317 Fax: Area Code 905 521 1297
defined as a systemic skeletal disorder characterized by a decrease in bone
mass and micro architectural deterioration of bone tissue, with a resultant
increase in bone fragility and susceptibility to fracture. Osteoporosis
frequently results in fractures of the vertebral spine, hip and wrist. Hip
fractures are a major cause of disability and death, with the mortality rate
from hip fractures estimated at 15-20% within the first year of
fracture. Hip fractures also account for the bulk of medical costs relating to
osteoporotic fractures. The total cost of hip fractures alone in Canada was
over 1.3 billion dollars a year in 1993.
is comprised of metabolically active cells', with bone turnover occurring in
discrete sites in the skeleton known as bone remodeling units. The osteoclast
is the cell responsible for bone resorption and the osteoblast for bone
formation. Under normal circumstances there is a coupled equilibrium of bone
formation and bone resorption. When bone formation is equivalent to bone
resorption, bone mass is maintained, however when resorption exceeds
formation, osteoporosis results.
is a silent thief, stealing bone with resultant fractures. Fractures typically
involve the hip, wrist, proximal humerus, ribs and vertebrae. Rib fractures
may occur after coughing or from a simple hug from a loved one. Fractures of
the hip and wrist typically occur after a fall with hip fractures having a 20%
mortality within the first three months following fracture. Vertebral
fractures may be asymptomatic, however this is the, exception rather than the
rule. On the other hand, patients with osteoporosis, do not have back pain due
to osteoporosis unless they begin to fracture. Vertebral fractures typically
occur in clusters and the presence of a fracture in any vertebra is a
significant risk factor for further fractures. When multiple vertebral
fractures occur, patients may become quite kyphotic, and are typically
described as having a dowagers hump. In rare instances after multiple
vertebral fractures the rib cage may sit upon the iliac crest. Abdominal
bloating, early satiety and symptoms of reflux then come into play.
Respiratory failure may be precipitated in those with under lying lung
disease. Acute back pain is often replaced by more chronic pain usually as a
result of increasing pressure being placed on the posterior elements of the
mass is the major determinant of osteoporotic fractures. Bone mass increases
during childhood and adolescence, peaks in the third or fourth decade and
declines thereafter at a rate of I % per year until the menopause when
accelerated rates of bone loss occur. During the first 5 years after the
menopause, it is not uncommon to see rates of loss averaging 3-5% per
year. Lifetime losses may reach as high as 30-40% in women and
20-30% in men.
who are said to be at greatest risk for osteoporosis are: postmenopausal women
and estrogen deficiency states including, premature menopause either as a
result of a natural menopause or oophorectomy, anorexia nervosa,
hyperprolactinemi and excessive exercise; thin, small stature; positive family
history; cigarette smoking; alcohol abuse; sedentary lifestyle; poor dietary
calcium intake and malabsorption as may occur in celiac disease; those of
white or asian race; and drugs including, anticonvulsants and cortico
steroids. Falls are a major risk factor for fractures therefore anything which
precipitates falls increases fracture risk.
is a disorder characterized by a failure to deposit calcium in the newly
formed organic matrix resulting in an excess of osteoid. There are a number of
different causes of osteomalacia. Intestinal malabsorption of vitamin D as is
seen with celiac disease is the most frequent cause of osteomalacia. Patients
with unsuspected celiac disease have presented with osteomalacia as there
initial presenting problem.
these patients may present with bone pain usually in the pelvis and lower
extremities, spine and ribs. It is dull and poorly localized, but clearly
arises from the bones rather than the joints. It is often made worse with
weight-bearing although never completely goes away with rest. Muscle
weakness and tenderness are most noticeable in the proximal lower limb girdle
and may vary from a slight abnormality to severe disability.
recently the only method of diagnosing significant bone loss was through plain
x-rays. Characteristic cod-fishing and compression fractures are
helpful in making a diagnosis of osteoporosis and may be useful aids in
identifying those with secondary osteoporosis. Looser
zones are diagnostic of osteomalacia while stress fractures may also be seen,
particularly in the feet.
factors such as increased risk of falling, changes in the mechanics of falls,
or qualitative changes in bone, may be important causes of fracture, bone mass
is the dominant factor in determining fracture risk. Bone mineral density and
bone strength are highly correlated. Since bone mass decreases with aging,
bone strength declines as well. As bone strength is a determinant of fracture
susceptibility, it follows that bone mineral density correlates with fracture
risk. It is not surprising then that a number of studies have shown that
fracture prevalence increases with a reduction in bone mass.
dietary calcium intake is required for the development and maintenance of a
normal skeleton. The importance of dietary calcium intake in attaining higher
bone mass and reduced hip fracture rates has been well reported. In
perimenopausal women calcium supplementation is probably of benefit, however
the effects of calcium are outweighed by the effects of estrogen deficiency.
In postmenopausal women calcium supplementation decreases rates of bone loss
and may be particularly important in those whose dietary calcium intake is
poor. In a randomized trial of calcium 1200 mg per day and vitamin D3800 IU
per day versus double placebo it was demonstrated that increases in hip bone
density and reductions in hip and non-vertebral fracture rates in the
elderly whose average age was 84 years. These studies demonstrate the
importance of calcium in maintaining bone health.
D and its analogues
exists over the use of vitamin D and its metabolites in the treatment of
osteoporosis. Doses of vitamin D3800IU per day and calcium 1200 mg per day has
been shown to reduce hip and non-vertebral fracture rates.
menopause,, bone turnover increases, with a greater increase in bone
resorption than formation. A review of the literature provides ample evidence
that postmenopausal estrogen therapy consistently exerts a protective effect
on bone loss'. A number of studies have conclusively demonstrated that
estrogen maintains bone mass. Withdrawal of ERT results in bone loss at a high
rate not unlike that seen immediately after going through the menopause.
dose response curve has been demonstrated in those commencing estrogen
replacement. Lower rates of loss occur with low dose estrogen, neither a gain
or loss with intermediate doses and a net gain in bone with medium to high
doses of estrogen.
in fracture rates have been demonstrated in a number of case-control
these trials, there is still a great deal of caution in recommending ERT for
postmenopausal females. The risk/benefit ratio of estrogen therapy must be
considered, however, prior to widespread use of ERT. Concern about breast
cancer exists. Although a large body of data exists on the effects of estrogen
replacement therapy and breast cancer, the results are inconsistent.
Short‑term users of estrogen do not appear to be at any increased risk
for breast cancer, however, there may be a slight risk for long‑term
users. There is good evidence demonstrating that unopposed ERT causes
endometrial cancer. It has been suggested, however, that the risk for
endometrial cancer may be substantially reduced by cyclic use of estrogen in
combination with progesterone therapy. Unfortunately, this is not acceptable
to many women who are at high risk for development of osteoporosis, for the
most part due to the unwanted return of menstrual bleeding. As a result,
continuous estrogen and progesterone therapy are currently being used. HRT may
also increase the risk for deep venous thrombosis (DVT). Despite all of these
concerns, there is evidence to suggest that all‑cause mortality is
reduced in -estrogen users when compared to non‑users.
relationship of estrogen to ischemic heart disease strongly suggests that
there is a protective role played by hormones. HRT probably acts at many
levels to prevent coronary artery disease including their ability to
favourably alter lipids and thrombotic mediators as well as a direct effect on
the reason that most women take HRT is a reduction in menopausal symptoms.
More recently the evidence that HRT may be of benefit in ‑preventing
memory loss may prove to be an even more important reason for its use.
is a Selective Estrogen Receptor Modulator or SERM. These are drugs that
attach to the estrogen receptor, affecting the receptor differently in the
different tissues. In bone raloxifene a positive effect, increasing bone mass
by reducing bone resorption and reducing vertebral fractures. Unlike estrogen
they do not stimulate breast tissue and in fact appear to reduce the risk for
breast cancer. Raloxifene does not stimulate the uterus and therefore does not
require concomitant progesterone and does not cause recurrence of menstrual
flow. Raloxifene can exacerbate menopausal symptoms though and should not be
used by those suffering from any symptoms of the menopause. Raloxifene does
reduce cholesterol levels without affecting triglyceride levels and as a
result it may be of benefit in reducing the risk of cardiovascular disease. On
the other hand Raloxifene does increase the risk of DVT. This risk is similar
to the risk on estrogen therapy.
are compound known to reduce bone resorption through the inhibition of
well designed prospective, randomized, double-blind
placebo-controlled trials have been .reported which showed the benefits
of etidronate on bone mass and fracture rates in women with postmenopausal
studies with alendronate have demonstrated significant increases in bone mass
general there is a 50% reduction in fractures. At this time alendronate has
the greatest amount of
stabilizes bone mass in both the axial and appendicular skeleton and because
of its analgesic effect is commonly used in the first several months after an
osteoporotic fracture. The availability of the nasal spray has increase its
overall patient acceptability. A recent study has demonstrated an increase in
spinal bone mass and a reduction in fracture rate in women with osteoporosis.