2019 Endocrine Society Guidelines: Postmenopausal Osteoporosis

Dr. Tashko reviews the 2019 Endocrine Society guidelines on postmenopausal osteoporosis, outlining risk categories, DEXA scan recommendations, FRAX scores' utility, fragility fracture implications, and optimal medication strategies.

Background – Osteoporosis Care in Maryland

As an osteoporosis specialist in Montgomery County, I focus on providing dedicated care to individuals with osteoporosis using an evidence-based approach.

Conveniently located in Rockville, my practice offers both virtual and in-person services, extending support to neighboring areas such as Chevy Chase, Bethesda, North Bethesda, Potomac, North Potomac, Gaithersburg, Germantown, Frederick, Silver Spring, Northern Virginia, Howard County, Anne Arundel, and the Eastern Shore of Maryland, ensuring comprehensive care.

Staying updated with the latest guidelines is crucial in osteoporosis management. Here, I summarize the 2019 Endocrine Society guidelines on postmenopausal osteoporosis.

Key Summary of the Guidelines

The Endocrine Society released its guidelines on postmenopausal osteoporosis in March 2019. The treatment algorithm is primarily based on fracture risk categories. Categories include three essential components:

  1. Fragility Fracture History
  2. T-scores
  3. FRAX scores

The society prefers bisphosphonates, especially alendronate (Fosamax) and zoledronic acid (Reclast), as the first-line therapy for women at high risk of fractures. Denosumab (Prolia) and anabolic hormones (Tymlos and Forteo) are also recommended.

If denosumab has been started, it should not be stopped without transitioning to another medication. Recent studies have shown a significantly increased risk of vertebral fractures within 12 months of discontinuation.

If bisphosphonates reduce the fracture risk to a low-to-moderate category, women could take a drug holiday after 3 to 5 years of use interruption. However, a drug holiday is not recommended for denosumab.

The Endocrine Society recommends anabolic hormones for postmenopausal women at very high risk of fragility fractures. Tymlos and Forteo can be used for up to 2 years due to concerns about developing osteosarcoma with longer use.

For women aged 60 or younger or within ten years of menopause, guidelines recommend cautious use of hormonal replacement therapy (HRT) or tibolone. Tibolone is unavailable in the United States. Patients should not have a history or be at increased risk of cardiovascular disease, blood clots, or breast cancer. Conversely, raloxifene or bazedoxifene could be used in those at risk for breast carcinoma.

As expected, calcium and vitamin D supplementation should be used as adjunct therapies for women in the high-risk category.

Adverse events from osteoporosis therapies ― osteonecrosis of the jaw (ONJ) and atypical femur fractures (AFF) ― have become public concerns in recent years. Although ONJ and AFF are real risks, the risk of fragility fractures from withholding pharmacological therapy far exceeds these potential side effects in high-risk and very high-risk women. Osteoporosis specialists need to inform patients of the benefit-to-harm ratio.

Dr. Tashko

2019 ES Osteoporosis

Dr. Tashko’s Simplified Risk Categories:

1. Low Risk (normal, pre-osteopenia)

  • No fractures
  • No elevated FRAX-score (<3% and <20%)
  • T-score of −1.0 or better

2. Moderate Risk (Osteopenia)

  • No fractures
  • No elevated FRAX-score (<3% and <20%)
  • T-score of –2.5 to -1.0

3. High Risk (Osteoporosis)

  • Prior fracture, or
  • T-score of −2.5 or worse, or
  • High FRAX-score (≥3% or ≥20%)

4. Very-High Risk (Severe Osteoporosis)

  • Multiple spine or severe fractures, and
  • T-score of −2.5 or worse
  • (FRAX-score adds no value)

JCEM, ES Guidelines, March 2019


  • We recommend treating postmenopausal women at high risk of fractures, especially those who have experienced a recent fracture, with pharmacological therapies, as the benefits outweigh the risks.
  • In postmenopausal women at high risk of fractures, we recommend initial treatment with bisphosphonates to reduce fracture risk:
    • Alendronate
    • Risedronate
    • Zoledronic acid, and
    • Ibandronate
      • Ibandronate is not recommended to reduce non-vertebral or hip fracture risk.
  • A bisphosphonate holiday:
    • It is operationally defined as a temporary discontinuation of bisphosphonate for up to 5 years.
    • This period may be longer depending on the bone mineral density and clinical circumstances of the individual patient.
    • The evidence is stronger for retention of benefits during a holiday for alendronate and zoledronic acid where there are randomized extension trials.
    • Discontinuation of denosumab is associated with a BMD decrease of 6.6% in the lumbar spine and 5.3% in the total hip within the first 12 months of treatment discontinuation
    • A drug holiday or treatment interruption is not recommended with denosumab
  • Raloxifene or Bazedoxifene use:
    • High Risk individuals
    • Patients with a low risk of DVT
    • Bisphosphonates or denosumab are not appropriate, or
    • Patients with a high risk of breast cancer
  • Estrogen use:
    • High Risk individuals
    • Women <60 years of age or <10 years past menopause:
    • At low risk of DVT
    • Bisphosphonates or denosumab are not appropriate
    • Have bothersome vasomotor symptoms
    • Have additional climacteric symptoms
    • Have no contraindications
    • Without prior MI or stroke
    • Without breast cancer;
  • Tibolone use
    • Women <60 years of age or <10 years past menopause:
    • At low risk of DVT
    • Bisphosphonates or denosumab are not appropriateHave bothersome vasomotor symptoms
    • Have additional climacteric symptoms
    • Have no contraindications
    • Without prior MI, stroke, or high risk for CV
    • Without breast cancer;
  • Monitoring bone turnover markers (serum C-terminal crosslinking telopeptide for antiresorptive therapy or procollagen type 1 N-terminal pro-peptide for bone anabolic therapy) is an alternative way of identifying poor response or nonadherence to therapy.

Endocrine Society Risk Categories:

  • “Low risk” includes no prior spine or hip fractures, a BMD T-score at the hip and spine both above −1.0, and 10-year hip fracture risk <3% and 10-year risk of major osteoporotic fractures <20%
  • “Moderate risk” includes no prior hip or spine fractures, a BMD T-score at the hip and spine both above −2.5, or 10-year hip fracture risk <3% or risk of major osteoporotic fractures <20%
  • “High risk” includes a prior spine or hip fracture, or a BMD T-score at the hip or spine of −2.5 or below, or 10-year hip fracture risk ≥3%, or risk of major osteoporotic fracture risk ≥20%
  • “Very high risk” includes multiple spine fractures and a BMD T-score at the hip or spine of −2.5 or below.

2019 ES - Osteoporosis 22.png

Osteonecrosis of the jaw (ONJ)

  • ONJ is a nonhealing wound in the oral mucosa with exposed bone that lasts >8 weeks, usually associated with an invasive dental procedure such as dental extraction or implantation but can occur de novo as well.
  • An international task force on ONJ reported on the association of bisphosphonate therapy and ONJ; the absolute risk of ONJ in osteoporosis patients was estimated to range from 1 in 10,000-100,000.
  • Higher doses and more frequent use of bisphosphonate and denosumab have been associated with greater ONJ risks in the oncology setting, but these patients have other risk factors such as cancer, chemotherapy, radiation therapy, and antiangiogenic therapies.
  • In osteoporosis patients on long-term oral bisphosphonate therapy, the risk of ONJ has been reported to be as high as 21 in 10,000 (or 0.21%) for patients on >4 years of therapy.
  • Tooth extraction in a patient exposed to bisphosphonate therapy carries a 0.5% risk of developing ONJ.
  • Currently, the American Dental Association does not recommend stopping bisphosphonates for dental procedures; however, if a tooth extraction or implant is planned or ongoing, initiation of potent antiresorptive therapy could be deferred until the area healed.
  • In contrast, the American Association of Oral and Maxillofacial Surgeons recommends a 2-month drug holiday for those who have taken >4 years of bisphosphonates.
  • Routine dental care is also important for the prevention of ONJ in patients treated with potent antiresorptive therapy.
  • Conservative management such as antibacterial mouth rinse is recommended as initial therapy for stage 0 to 2 ONJ, whereas surgical debridement and resection is recommended for stage 3 ONJ.
  • Although there have been case reports of using teriparatide as well as other therapies (such as platelet-rich plasma, low-level laser irradiation, and bone morphogenic protein) in the successful treatment of ONJ, controlled studies are needed to establish efficacy of these therapies.

Atypical Femoral Fractures (AFF)

  • AFFs are insufficiency stress fractures of the femoral shaft first noted in case reports in about 2007 that suggested a possible association with bisphosphonate use. These fractures have specific radiological characteristics that have been formalized in a case definition by the ASBMR based on radiographic criteria and low trauma.
  • AFFs have been most studied in relationship to bisphosphonate use but have also been noted with other osteoporosis medications including denosumab, odanacatib, and romosozumab. Patients often present with pain or aching in the thigh or groin with or after weight-bearing activities.
  • The pathogenesis of these fractures is not understood, although a number of hypotheses including factors related to femur shape, genetics, and ethnicity have been advanced.
  • A large number of epidemiologic studies focusing on bisphosphonate usage and duration have been published. However, many have not had assessments of individual radiographs and instead relied on femoral shaft fractures as defined by ICD codes from population registries.
  • Unfortunately, this endpoint is problematic because <5% of these femoral shaft fractures would have met AFF criteria if radiographs had been evaluated. This nonspecific endpoint could have masked AFF increases in these studies, as well as in a meta-analysis of AFFs published in 2013, which included many such studies.
  • Calculation of AFF incidence restricted to studies with radiographic evaluation shows incidence to be very low.
  • For example, a study in Sweden using national data for women and men >55 years of age for 2008 to 2010 showed that among a total of 50,325 femur (hip or femoral shaft) fractures, only 172 (about 3 AFFs per 1000 hip fractures) met ASBMR criteria.
  • A similarly low ratio of AFFs to hip fractures was shown in a study performed in Kaiser Permanente Northwest. This study showed very low AFF incidence in their population (about 5 per 100,000 person-years) compared with an almost 100-fold higher incidence of hip fractures (300 to 400 per 100,000 person-years).
  • Despite low incidence rates, studies with radiographic assessment have shown strong increases in AFFs with longer duration of bisphosphonate use. For example, one widely cited study from a large health maintenance organization in California of people >45 years of age (∼1.8 million) showed AFF risk (unadjusted) for 2 years of use to be ∼3 per 100,000 person-years, increasing to ∼20 per 100,000 person-years with 5 years of use and ∼50 per 100,000 with >8 years of use.
  • Despite this increase, risks of hip and other osteoporotic fractures that can be prevented by treatment are much higher, suggesting a positive benefit-risk ratio even for long-term treatment, particularly in older women at highest risk of hip and other osteoporotic fractures.
  • Whereas one analysis of benefit vs risk for bisphosphonate treatment of 3 years showed that treating 1000 osteoporotic women would prevent 100 fractures, including 11 hip fractures, while causing about 0.1 AFF, similar data for longer-term treatment are not available, and the consistent increase shown for treatment beyond 5 years suggests consideration of AFF risk in treating patients for >5 years.
  • As discussed in section 2, the ASBMR long-term has proposed that the risk could be reduced by taking a “holiday” from oral bisphosphonates after 5 years and from IV bisphosphonates after 3 years in patients who are at low-moderate fracture risk.
  • Specific recommendations for bisphosphonate holidays are discussed in “Bisphosphonates”. There are insufficient data about the relationship of long-term denosumab to AFF risk to make a recommendation about duration of use.
Dr. Tashko is an ABIM board-certified endocrinologist with additional certifications in lipidology, hypertension, and obesity medicine. He delivers personalized, holistic care to patients in Montgomery County, Maryland.