Osteoporosis in Menopause

By Jyothsna Bandaru, MD, FACP

INTRODUCTION:

Osteoporosis is a generalized skeletal disorder characterized by impaired bone strength, that increases the risk of fractures, most importantly of the spine and hip.

These and other osteoporosis- related fractures occur most commonly in the older postmenopausal women and are often lifealtering events; however, the bone loss leading to osteoporosis, is most marked during the menopause transition and early menopause.

Younger post-menopausal women with wrist fracture, who have osteopenia or normal BMD, are at increased risk for future fractures, even if they do not have osteoporosis at the time of fracture.

PATHOPHYSIOLOGY:

In adults, there is a constant change of bone tissue, through a process called bone remodeling, where old bone is resorbed (removed) by osteoclasts and replaced by new bone by osteoblasts.

In young healthy women, the resorption and formation components of bone remodeling are balanced; the amount of old bone resorbed is replaced with an almost equal amount of new bone. As a result, bone mass is usually quite stable in healthy premenopausal women.

However, at the time of menopause, in response to estrogen deficiency, bone resorption becomes more rapid exceeding the ability of osteoblasts to replace new bone, resulting in bone loss. The imbalance in remodeling continues into advanced age, when an additional deficit in osteoblast function limits the rate of additional bone formation.

As bone loss occurs in the trabecular component of bone, especially in the spine and ends of long bones, the once thick and numerous trabeculae become thinned and perforated and often completely resorbed, leaving empty spaces in the place where bone tissue existed. The imbalance in bone remodeling can be accentuated by very sedentary lifestyle, often resulting in increased bone loss in elderly inactive women.

DIAGNOSING OSTEOPOROSIS:

The measurement of BMD by dual energy X-ray absorptiom- etry (DXA) is the principal clinical tool to assess skeletal health. T-scores are used to make the diagnosis of osteoporosis in postmenopausal women.

The Z-score has limited value in postmenopausal women but is the preferred method of expressing BMD values in premenopausal women.

WHO defines osteoporosis in postmenopausal women as a BMD T-score value of –2.5 or lower, at the lumbar, femoral neck or total hip by DXA testing, whereas T-score of –1 to –2.49 is considered as osteopenia.

The diagnosis of osteoporosis is made in premenopausal women who have BMD Z-score of –2.0 and a history of fragility fracture.

Other methods of bone mineral density assessment include quantitative CT, densitometric measurements of the heel or fingers, and noninvasive ultrasound measurements at several skeletal sites.

PREVALENCE:

Between 40%- 50% postmenopausal women experience an osteoporosis related fracture during their lifetimes.

Vertebral fractures are associated with acute and chronic pain, height loss, and deformity and adversely affected ambulation, pulmonary function, and ability to perform routine chores.

Fear of falling after having a fracture limits socialization and physical activity, contributing to the effect of fractures on development of frailty.

RISK FACTORS:

Advanced age

Thinness

BMD in healthy women is strongly correlated with body weight. So thin women have lower BMD compared to heavy women. Genetic differences - In general, US Asian women have lower BMD than white women, whereas BMD in black women is generally higher.

Smoking - Possible explanations include women who smoke are generally thinner, have earlier menopause and lower serum estra- diol levels than nonsmokers.

History of fracture, prior fragility fracture

Low BMD

Age

Excessive alcohol intake

Parental history of hip fracture

Diseases and drugs – DM2, obesity, proton pump inhibitors

FRAX is the 10-year probability of hip fracture or major osteoporotic fracture (hip, proximal humerus, distal radius and symptomatic spine fractures). FRAX is appropriate for use in postmenopausal women aged 40 to 90 years.

INDICATION FOR BMD TESTING:

All postmenopausal women with medical causes of bone loss, hx fragility fracture, or age>= 65

CLINICAL EVALUATION OF WOMEN WITH OSTEOPOROSIS:

A complete medical evaluation, including a detailed history of other diseases and medications, previous fractures and family history, a thorough physical examination and routine laboratory testing should be performed in all patients with osteoporosis before initiating therapy.

MANAGEMENT OF OSTEOPOROSIS:

• Comprehensive fall prevention programs, including home safety, exercises to promote strength and balance, correcting visual impairment, and appropriate use of walking aids may reduce fall frequency but have not been shown to reduce fracture risk.

• Correcting the deficiencies of calcium and vitamin D.

• In otherwise healthy postmenopausal women, including those with osteoporosis, the average serum 25-OH D level is about 20ng/ml.

• In fall-prone elderly patients, who were losing weight, higher protein intake was associated with reduced fall frequency.

• Magnesium deficiency is uncommon in healthy patients with normal diets. Although providing magnesium supplements to patients with malabsorption may be warranted, routine magnesium supplementation cannot be recommended.

• In a small randomized clinical trial in postmenopausal women, adding vit K2 to risedronate had no effect on BMD or fractures.

• There is no compelling evidence for beneficial effects of boron, zinc, black cohosh, berberine, or dehydroepiandrosterone (DHEA) on bone density or fracture risk in postmenopausal women.

PHARMACOLOGIC THERAPY:

North American osteoporosis guidelines suggest treating the patients with low BMD with 10-year fracture probability of major osteoporosis fracture of 20% or more, or hip fracture risk of 3% or higher. No treatment “cures” osteoporosis.

The beneficial skeletal effects of most osteoporosis drugs wane quickly on stopping treatment. Hence, long-term treatment is required for this chronic disorder.

Beginning estrogen more than 10 years beyond menopause is not recommended due to safety concerns on CV health. The beneficial skeletal effects of estrogen abate within a few months of stopping therapy. Switching from estrogen to alendronate (or other bisphosphonates or denosumab) prevents the rebound in remodeling and rapid bone loss.

Raloxifene is an option for younger postmenopausal women with osteoporosis at risk for vertebral fracture, but no concern for hip fracture, without risk factors for venous thrombosis, vasomotor symptoms, and with concerns on breast cancer risk.

The four drugs in the class of bisphosphonates (alendronate, risedronate, ibandronate, zoledronic acid) are aminobisphosphonates, which are more potent than the original bisphosphonates. Ibandronate reduced spine fracture risk, but no overall effect on nonvertebral or hip fracture risk.

Diffuse bone, muscle or joint pain of unknown mechanism are described with both oral and IV bisphosphonates.

Poor oral hygiene and invasive dental procedures are risk factors for osteonecrosis of the jaw (ONJ).

Patients on bisphosphonate therapy for more than 3 years should be cautioned to report new thigh or groin pain, so that appropriate radiology evaluation can be undertaken.

Bone mineral density in the hip region plateaus and then remains stable after about 5 years of bisphosphonate therapy. After 5 years of treatment in women at high fracture risk, switching to denosumab might result in additional gains in BMD.

Skin rash and infection occurred more frequently with denosumab than placebo.

As with stopping estrogen, switching to a bisphosphonate is suggested if denosumab therapy is stopped.

Because of possible association with increased cancer risk, nasal calcitonin is marketed with caution in American prescribing information.

Teriparatide is a recombinant 1-34 N-terminal fragment of PTH. Adverse events with teriparatide include transient hypercalciuria, hypercalcemia, dizziness, and muscle pain. Switching to a bisphosphonate or denosumab is advised to preserve or improve BMD, when stopping therapy.

Abaloparatide is a synthetic analog of parathyroid hormonerelated peptide (PTHrP). Both these agents carry a blackbox warning about potential risk of osteosarcoma due to studies in rats.

Monitoring renal function with bisphosphonate use and serum calcium with teriparatide use is suggested.

In summary, rapid bone loss which almost always occur in postmenopausal women can lead to osteoporosis and subsequently high fracture risk. The benefit-risk ratio for denosumab, bisphosphonates, raloxifene is very favorable during the first several years of therapy. Continued on page 20