Postmenopausal osteoporosis is a major health problem hiding in plain sight. I say this because we see patients with osteoporosis and osteoporotic fractures every day in our clinics, but only a small percentage of these patients are properly evaluated and started on therapy.
There are 10 million patients diagnosed with osteoporosis in this country, and 80% of them are women. Women over the age of 50 have a 54% likelihood of having an osteoporotic fracture in their lifetime.
When these women fracture, however, they are seldom properly evaluated, as less than 25% of women 67 or older with a hip fracture get a bone mineral density evaluation. This is very costly to the U.S. healthcare system. The cost of treating hip fractures was $57 billion in 2018 and is projected to be $95 million by 2040. These are only dollar amounts and do not take into consideration the cost of pain, disability and loss of independence.
Appropriately screening for osteoporosis and then starting and monitoring response to therapy is critical.The screening tools we have are bone mineral densitometry (BMD) and the fracture risk assessment tool (FRAX). The most common bone densitometry is dual x-ray absorptiometry or DXA. FRAX is a survey that can be obtained online, and the FRAX score gives the patient’s 10-year risk for both major osteoporotic fractures and hip fractures.
Anyone with a 20% risk of major osteoporotic fracture or a 3% risk of hip fracture should be further evaluated. So who should be screened? Any postmenopausal woman over the age of 50 should at least get a FRAX score, and my threshold for getting a DXA on these women is very low. All women over the age of 65 should have a DXA assessment. Also, there are several special populations that should be screened earlier with DXA, such as patients who have fractures, hypercalcemia, malabsorption of calcium (Celiac Disease), hyperparathyroidism, vitamin D deficiency, Cushing’s disease or are taking drugs that cause skeletal harm like steroids.
The American Association of Clinical Endocrinologists (AACE) have four criteria for making the diagnosis of osteoporosis based on T-scores obtained from DXA, clinical data and FRAX scores. If a patient meets any one of these four criteria, they have osteoporosis:
- T-score of -2.5 or below in the lumbar spine, femoral neck, total proximal femur or 1/3 radius.
- Low trauma spine or hip fracture (regardless of bone density)
- T-score between -1.0 and -2.5 and fragility fracture of proximal humerous, pelvis or distal forearm
- T-score between -1.0 and -2.5 and high FRAX fracture based on country specific thresholds.
Once the diagnosis of osteoporosis has been made, an assessment should be conducted to rule out secondary causes with a CMP, CBC, 25-OH Vit D, PTH, phosphate, TSH, celiac antibodies, serum and urine electrophoresis and 24-hour urine for calcium, sodium and creatinine so that a proper treatment plan can be mapped out.
As with any chronic disease, therapy consists of appropriate lifestyle changes and pharmacologic therapies. The lifestyle changes should include consuming a balanced diet and ensuring adequate calcium intake (1200 mg daily for women over 51) and vitamin D intake (1000 to 2000 units daily). Patients should be on an exercise regimen that includes weight-bearing exercise and balance exercises to prevent falls. Patients should stop smoking and limit their alcohol and caffeine. Homes should be fall-proofed by anchoring rugs, minimizing clutter, removing loose wiring, using non-skid mats, installing appropriate handrails and making sure the house is well lit, especially around hallways, stairs and entrances. Patients should be encouraged to wear sturdy, low-heeled shoes.
In terms of pharmacologic therapy, there are multiple drugs approved to treat osteoporosis. There are two broad categories of drugs. Anti-resorptives like the bisphosphonates, calcitonin, Selective estrogen receptor modulators (SERMs) and receptor activator of nuclear factor kappa-Î’ (RANK) ligand inhibitors slows osteoclast activity. The anabolics like the PTH analogues and the new novel sclerostin inhibitor promote osteoblast activity. It should be pointed out that estrogen replacement therapy is approved for the prevention of but not treatment of osteoporosis.
See Table 1 at the bottom of this article  for the names, dosages and routes of administration for the drugs approved for the treatment of osteoporosis.
Choosing a therapy for osteoporosis depends on the severity of the disease. AACE stratifies osteoporosis into patients that are at high risk of fracture and those that are very high risk of fracture. Those at high risk have had no previous clinical fractures and are at low risk of falling. Those at very high risk have recently fractured, have fractured while on treatment, have multiple fractures, fracture on drugs causing skeletal harm, have a T-score below -3.0, or have high risk of falling.
Initial therapy for high-risk patients should be one of the bisphosphonates or Denosumab. For the very high risk, I prefer a course of an anabolic agent followed by an anti-resorptive agent once the course of anabolic therapy is complete.
Treatment for osteoporosis must be tempered by overall effects and the patient’s ability to take the drug. Patients must be upright 30-60 minutes after taking an oral bisphosphonate, and it must be taken 60 minutes before any food or other medication. All bisphosphonates should be avoided in patients with low eGFRs.
Bisphosphonates have been associated with bone, muscle and joint complaints as well as osteonecrosis of the jaw (ONJ) and atypical proximal femoral fracture (AFF). Although the incidence of ONJ and AFF are very rare, patients are frightened by these effects. Denosumab causes rash, injection site problems, hypocalcemia in low vitamin D patients and have a rate of ONJ and AFF similar to the bisphosphonates. The PTH activators cause nausea, orthostatic hypertension and hypercalcemia, which are usually mild and transient. The black box warning about osteosarcoma limits the course of therapy to only 2 years, and they should not be used in patients who have received radioactive therapy.
Lastly, the new sclerostin inhibitor, Romosozumab, has a black box warning about use in patients with known cardiovascular events. The anabolic effect of Romosozumab wanes after 12 months limiting it to a one-year course of therapy.
Patients being treated for osteoporosis need to be monitored yearly with DXA. For those at high risk on bisphosphonates, if BMD is stable to increasing and they have had no fractures, then they can be offered a drug holiday after 5 years of oral or 3 years of IV therapy. They should continue to be monitored and restarted on therapy if BMD declines. If the patient’s BMD worsens or they fracture, they should be switched to an anabolic therapy if possible.
Patients at very high risk should be monitored yearly throughout the course of anabolic therapy and transition to a bisphosphonate or Denosumab therapy. It should be noted at this time that Denosumab therapy cannot be stopped abruptly, as there is a rapid decline in BMD. Patients receiving Denosumab need to be transitioned to a bisphosphonate or an anabolic that can be tapered off.
In summary, postmenopausal osteoporosis must be recognized early to prevent fracture. All women over 50 are at risk and should be screened with FRAX and DXA. Pay special attention to patients with suspicious fractures or that are on medications that cause skeletal harm. All women at risk should be on appropriate amounts of calcium and vitamin D and instructed in appropriate lifestyle changes and full prevention.
Women with high-risk osteoporosis should be placed on anti-resorptive agents, and those with very high risk should be given a course of anabolic therapy followed by an anti-resorptive. Patients should be monitored yearly while on therapy. Do not let this high-risk group go unevaluated, and when osteoporosis is diagnosed, treat appropriately and monitor yearly.
