Updated AACE/ACE Guidelines for the Diagnosis and Treatment of Postmenopausal Osteoporosis: What Do Clinicians Need to Know?

OSTEOPOROSIS text written on notebook with stethoscope, syringe and pills. Medical and health care concept.
The ACE and AACE released a 2020 update to their clinical practice guidelines for the treatment and diagnosis of postmenopausal osteoporosis.

In collaboration with the American College of Endocrinology (ACE), the American Association of Clinical Endocrinologists (AACE) has released a 2020 update to the clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis. These guidelines were published in Endocrine Practice.1

The guidelines were developed in accordance with the AACE Protocol for Standardized Production of Clinical Practice Guides, Algorithms, and Checklists-2017 Update.2 Clinical recommendations were based on a systematic review of relevant studies and were graded based on the evidence level of the supporting literature.

The guidelines executive summary contains 21 grade A (40%), 24 grade B (46%), and 7 grade C recommendations (14%). Of the 368 citations on which the recommendations are based, 69.5% were considered of intermediate or higher quality evidence level. Major updates from previous guidelines are summarized below and include the stratification of patients according to risk features, recommendations regarding the new anabolic agent romosozumab, and transitions between therapeutic agents, including denosumab.

Stratification According to High-Risk and Very-High-Risk Features

Patients considered to be at very high risk for fracture include those with a recent fracture (within the previous 12 months), those who experience fractures while receiving approved osteoporosis therapy, those who experience multiple fractures, and those who experience fracture while receiving drugs that cause skeletal harm, such as long-term corticosteroids. In addition, patients at very high risk are those with a T-score <-3.0, individuals considered to be at high risk for falls or who have a previous history of injuries associated with falling, and those with very high fracture probability as assessed by FRAX® (Fracture Risk Assessment Tool) or another validated fracture risk algorithm.

More aggressive treatment may be considered in patients at very high risk for fracture.

The guideline task force noted that FRAX may underestimate the fracture risk for patients with diabetes. Rheumatoid arthritis may be entered into the FRAX algorithm as a surrogate for the fracture risk associated with type 2 diabetes, or trabecular bone score may be used to adjust FRAX scores for more accurate risk prediction.

For patients at very high risk for fracture, abaloparatide, denosumab, romosozumab, teriparatide, and zoledronate should be considered as initial therapy.

Patients who have been diagnosed with osteoporosis but not at very high risk for fracture should be considered high-risk patients. For most patients at high risk for fracture, alendronate, denosumab, risedronate, and zoledronate are appropriate initial therapeutic options.

We interviewed Gary Edelson, MD, board member for the National AACE organization, past president of the AACE Michigan Chapter, and endocrinologist with Associated Endocrinologists in Farmington Hills, Michigan, to learn more about how clinicians can apply the updated recommendations to their practice.

“The guidelines also make a differentiation on when to switch from an oral therapy to parenteral (injectable or [intravenous]) therapy and note that parenteral therapy should always be followed by an antiresorptive agent,” stated Dr Edelson. “The guidelines recommend abaloparatide, denosumab, romosozumab, teriparatide and zoledronate be considered for patients unable to use oral therapy and as initial therapy for patients at highest fracture risk.”

“For women at high risk for fracture, I would consider new therapies, especially anabolics like abaloparatide or romosozumab. I’m really excited to see these anabolic therapies included in the updated guidelines, because I use them quite a bit for my high-risk patients,” he added.

Romosozumab for Postmenopausal Osteoporosis

Romosozumab is a monoclonal antibody against sclerostin that promotes osteoblast activity. Use of romosozumab is associated with pronounced increases in bone density and associated with both modeling and remodeling activity in the bone.

The guideline task force recommended that romosozumab be considered a “rescue drug” for patients at very high risk for fracture, particularly those who were previously treated with teriparatide or abaloparatide. Romosozumab can also be used in patients with previous radiation exposure.

Romosozumab is not recommended in patients at high risk for cardiovascular events or who have had recent myocardial infarction or stroke.

Treatment with romosozumab should be limited to 1 year and should be followed up with a drug indicated for long-term use, such as bisphosphonate or denosumab, which may prevent bone density decline and loss of fracture efficacy.

Romosozumab is currently not recommended as a preventative option for postmenopausal osteoporosis.

“The inclusion of these additional medications, including abaloparatide, denosumab, romosozumab, teriparatide, and zoledronate, affirms for clinicians the importance of treating women with postmenopausal osteoporosis.” said Dr Edelson. “It is important to note that these guidelines recommend sequential therapy upon discontinuation of an anabolic agent — following treatment with [any] anabolic agent (eg, abaloparatide, romosozumab, or teriparatide) with a bisphosphonate or denosumab.”

Transitions Between Therapeutic Agents

According to the updated guidelines, patients transitioning from denosumab or anabolic agents such as romosozumab may receive oral bisphosphonates or another antiresorptive agent when the course of treatment is complete. This may help to avoid bone loss after discontinuing use of the drugs.

Romosozumab therapy can be continued for up to 1 year before sequential therapy, abaloparatide or teriparatide therapy for up to 2 years, and treatment with zoledronate for up to 6 years if the patient remains stable. If progression of bone loss or fracture occurs, patients treated with zoledronate may be transitioned to another anabolic agent before beginning antiresorptive therapy.

Denosumab may be continued until a patient is no longer considered to be at high risk for fracture. If denosumab treatment is discontinued, patients should be transitioned to an alternative antiresorptive therapy. Switching from denosumab to an anabolic agent is not recommended because of potential loss of hip bone mineral density.

While drug holidays may be considered after long-term use of oral bisphosphonates, they are currently not recommended for nonbisphosphonate antiresorptive drugs such as denosumab.

Recommendations for transitions from therapeutic agents are outlined in the AACE/ACE 2020 Postmenopausal Osteoporosis Treatment Algorithm available at the end of the 2020 guideline update.


“The updated AACE guidelines provide a simple and clinically applicable approach for clinicians to care for and treat patients with postmenopausal osteoporosis. The updates place greater emphasis on the importance of case recognition and diagnosis than the previous guidelines, which were published in 2016,” Dr Edelson noted.

“The guidelines also include more of an emphasis on higher risk patients and the need for appropriate therapy,” he added. “They give clinicians tools to approach patients when they may not be sure what drugs to use, if any. Since the last guidelines update, there have been several new medications approved by the United States Food and Drug Administration that are now included in the treatment recommendations, including abaloparatide and romosozumab.”

“Postmenopausal osteoporosis is a silent disease, often displaying no signs or symptoms until a fracture occurs, leaving many patients undiagnosed and untreated,” stated Dr Edelson. “I’m hopeful that these important updates to the guidelines will help women with postmenopausal osteoporosis get the treatment they need and that healthcare providers will more readily identify the signs and symptoms of postmenopausal osteoporosis, and refer patients to an endocrinologist or bone health specialist when necessary.”


1. Camacho PM, Petak SM, Binkley N, et al. American Association of Clinical Endocrinologists/American College of Endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis—2020 update. Endocr Pract. 2020;26(1):1-46.

2. Mechanick JI, Pessah-Pollack R, Camacho P, et al. American Association of Clinical Endocrinologists and American College of Endocrinology protocol for standardized production of clinical practice guidelines, algorithms, and checklists – 2017 update. Endocr Pract. 2017;23(8):1006‐1021.