OSTEOPOROSIS
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

Introduction

Osteoporosis is 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.

Pathophysiology

Bone 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.

Clinical Presentation

Osteoporosis 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 spine.

Risk Factors

Bone 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.

Those 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.

Differential Diagnosis

Osteomalacia 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.

Clinically 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.

Diagnostic Studies Radiographic Assessment

Until 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.

Bone Mass Measurement

While 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. 

Prevention and Treatment

Calcium

Adequate 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.

Vitamin D and its analogues

Controversy 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.

Hormone Replacement Therapy

At 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.

A 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.

Reductions in fracture rates have been demonstrated in a number of case-control studies.

Despite 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.

The 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 vasculature.

Clearly 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.

Raloxifene

Raloxifene 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.

Bisphosphonates

Bisphosphonate are compound known to reduce bone resorption through the inhibition of osteoclastic activity.

Two 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 osteoporosis.

Numerous studies with alendronate have demonstrated significant increases in bone mass at the spine and hip. Of greater significance are the reductions seen in hip, spine and wrist fractures.

In general there is a 50% reduction in fractures. At this time alendronate has the greatest amount of evidence demonstrating treatment benefit and should be considered the treatment of choice for those with osteoporosis. Alendronate has also been shown to be of benefit in the prevention of osteoporosis. In severe osteoporosis the combination of alendronate with either HRT or Raloxifene has greater benefit than either drug alone in increasing bone mass.

Calcitonin

Calcitonin 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.

Dr. Adachi

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