#277 Bone Up on Osteoporosis in Primary Care with Dr. Carolyn Crandall

May 31, 2021 | By Emi Okamoto

Bone up on osteoporosis in primary care! Don’t let osteoporosis sneak up on your patients with a vertebral fracture or a hip fracture! Make no bones about your osteoporosis knowledge, from knowing when to screen your patients to selecting a treatment that matches your patient’s lifestyle. Join us as we discuss these topics and more with osteoporosis expert and internal medicine physician, Dr. Carolyn Crandall (UCLA).
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Credits

• Producer: Isabel Valdez, PA-C
• Show Notes: Isabel Valdez, PA-C
• Infographic: Isabel Valdez, PA-C
• Cover Art: Kate Grant MD
• Hosts: Isabel Valdez, PA-C; Matthew Watto MD, FACP; Paul Williams MD, FACP   
• Editor: Emi Okamoto MD FACP and Leah Witt, MD  (written materials); Clair Morgan of nodderly.com
• Guest: Carolyn Crandall MD

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Show Segments

• Intro, disclaimer, guest bio
• Guest one-liner
• Picks of the Week
• First Case from Kashlak
• Definitions of Osteoporosis and Low Bone Density (formerly Osteopenia)
• Patient Counseling on Treatment Side Effects
• Frequency of Testing
• Dental Clearance 
• CKD and Osteoporosis Treatment 
• Prevention
• Vitamin D and Calcium
• Take-home Points and Outro

Osteoporosis in Primary Care Pearls

1. The primary goal of osteoporosis treatment is to reduce hip fractures.
2. In cases where both osteoporosis and osteopenia/low mineral density are listed in the results, use the lowest T-score to make the final diagnosis.
3. If your young postmenopausal patient presents with a wrist or forearm fracture, think about screening them for osteoporosis. 
4. Set expectations regarding treatment duration and rarity of adverse effects such as osteonecrosis of the jaw.
5. Bone mineral density testing can be repeated 5 years after treatment starts according to ACP.
6. Since evidence is lacking to determine treatment duration and monitoring after treatment, expert opinion and patients’ personal risks can be used to arrive at the best possible option. 
7. Uncomplicated GERD is not a contraindication for oral bisphosphonates and there are ways to mitigate the symptoms. 
8. Denosumab discontinuation has been associated with an increased risk of fractures, and after discontinuation it is recommended that patients transition to another antiresorptive treatment.
9. Romosozumab carries the added risk of major cardiovascular adverse events. 
10. The COVID pandemic interrupted treatment for many patients who could not receive their injections, thus alternative oral treatments were considered alternatives.
11. Routine dental work can be done without interrupting the use of bisphosphonates and major dental work, especially in a patient with major risk factors, should be done before starting osteoporosis treatment whenever possible. 
12. Treatment recommendations for patients with CKD are lacking evidence. 
13. Vitamin D and calcium should be replenished to sufficient levels (not excess). 

Osteoporosis in Primary Care Show Notes 

Definition of osteoporosis and low bone density (formerly osteopenia)

Osteoporosis is characterized by low bone mass, microarchitectural disruption and increased fragility. In conversation with patients, Dr. Crandall describes osteoporosis as having “delicate bones or fragile bones” that increase the risk of breaks or fractures. 

Osteoporosis diagnosis is made in two ways

• T-score of less than or equal to -2.5 on DXA
• Fragility fracture or minimal trauma fracture, particularly of the hip or spine regardless of bone density. 

Major osteoporotic fractures (MOF) are defined by FRAX as proximal humerus, distal forearm/wrist, hip, and spine (clinical).  

Osteopenia is now called ‘low bone density’ and is defined as having a T score between -1.0 and -2.5.  The majority of the fractures happen in patients with low bone density not because they are at higher risk for fracture but because there are more people with this diagnosis (Pasco, 2006).

Fractures of the wrist and forearm occur more often than hip fractures in younger postmenopausal women.  Screening with a bone density test in these patients is advisable since they have a 20% chance of another fracture in 10 years  (Crandall, 2015). 

Patient counseling on treatment and side effects 

Dr Crandall suggests starting the treatment conversation by informing the patient of the expected duration of treatment.  Hip fracture mitigation should be the gold standard we strive towards when selecting treatment (Berry, 2019).   She recommends framing the discussion as a balance between the odds of having a hip fracture compared to the risk of having rare medication adverse effects (Lo, 2010).  Providers should acknowledge that the risk of osteonecrosis of the jaw with bisphosphonates is as low as 1 in 10,000 to 1 in 100,000 when discussing the first-line treatment options for osteoporosis (Khosla, 2007; Adler 2015)

Bone Mineral Density Surveillance and Treatment Adherence  

Precision challenges

Dr. Crandall mentioned that changes in bone mineral density of 3-6% at the hip or 2-4% at the spine could be due to the precision error of the test itself.  For this reason, it is important to use the same machines to track bone mineral density, if possible.   She also suggests reviewing the bone mineral density report carefully for a statement that describes whether the change is significant on the specific machine compared with previous scans to prevent errors in treatment. 

Screening intervals for those without osteoporosis

Evidence is insufficient to determine the frequency of screening bone mineral density (Viswanathan, 2018). If baseline bone mineral density is normal in an otherwise healthy older person, frequent serial imaging is not recommended unless the patient is at risk for bone loss due to a secondary cause.  Monitoring patients with normal bone mineral density does not have to be done frequently in part because bone loss occurs at about 1% a year which is less than the typical measurement error of the machine. Frequency of monitoring should be based on the patient’s baseline risk. For example, expert opinion for retesting a postmenopausal woman that is mildly osteopenic could be 5 years.

Bone mineral density testing for those with treatment

Based on ACP guidelines, bone mineral density testing can be repeated after 5 years of treatment, suggesting that treatment for post-menopausal women be 3 to 5 years depending on the drug of choice ie: five years of oral bisphosphonate treatment vs three years of treatment with zoledronic acid or denosumab. 

The role of image surveillance during drug holidays is unknown and could be based on the medical expert’s practice and/or the patient’s risk level. 

Treatment adherence

Repeat bone mineral density imaging while on treatment does not reduce the fracture risk (Berry, 2013) nor does it increase the patient’s adherence to medication. To monitor for adherence, Dr. Crandall recommends it’s best to have a conversation with the patient about the treatment such as having the patient repeat the dosing instructions. Gastrointestinal intolerance to bisphosphonates is one of the most reported side effects yet studies have shown that when patients are rechallenged with placebo, the tolerance is similar (Eisman, 2004). She mentions bisphosphonates can be used in uncomplicated cases of reflux. Additionally, she uses GI side effects as a segway to select dosing frequency with the patient such as daily vs annually.

Labs

Our expert recommends routine labs ahead of treatment such as renal function, hepatic panel, TSH, calcium (if not part of another panel already), and 25-hydroxy vitamin D.  Dr. Crandall does think about testing other secondary causes such as multiple myeloma, Cushing’s (if Cushingoid appearance), celiac disease (if diarrhea), and other secondary causes when past history may be suggestive. 

Low calcium or vitamin D should be repleted before starting bisphosphonates.   

Treatment 

Bisphosphonates

Bisphosphonates (alendronate, risedronate, zoledronic acid) or the bone-modifying monoclonal antibody  denosumab (see below) are all considered to be first line treatments since they are proven to reduce hip fractures (Qaseem, 2017). Based on ACP guidelines, post-menopausal women should receive five years of oral bisphosphonate treatment or three years of treatment with zoledronic acid. Duration of treatment after the 5 year mark depends on several factors including comorbidities or changes in the patient’s health status. Medical expert opinion: Consider extending treatment in patients at high-risk for spine fracture or hip fracture another few years (Black, 2006). Dr. Crandall has patients report back how to take their oral bisphosphonate: first thing in the morning, on an empty stomach, without other pills (e.g. calcium), and with a full glass of water.

Denosumab

Duration of use of denosumab has not been studied to date. The offset of action of denosumab is quick when it is stopped thus the risk of vertebral fractures increases after it is discontinued (Tsourdi, 2021).  To date, studies are lacking to determine how soon to restart treatment after the cessation of denosumab and to know which treatment should be used next. Regardless, treatment should be continued with another agent such as an antiresorptive medication (AACE, 2020; Ensrud, 2020). 

Romosozumab

Romosozumab targets sclerostin and increases bone formation and it is approved for postmenopausal women at high risk for fracture such as patients with a history of osteoporotic fractures or who have failed other therapies (Cosman, 2017).  Romosozumab is contraindicated in patients with hypercalcemia and has been found to pose a risk for major adverse cardiovascular events as well as osteonecrosis of the jaw and atypical femoral fractures in the studies (Fixen, 2021). Dr. Crandall points out that bisphosphonates/denosumab were used following romosozumab so it is difficult to tease out what medications may have caused the adverse events. 

Parathyroid Hormone Analogs 

The ACP has not recommended teriparatide and abaloparatide as first-line treatment.

The Impact of the COVID Pandemic and Osteoporosis Treatment 

With the interruption of subcutaneous treatments such as denosumab and romosozumab during the COVID pandemic, the use of oral bisphosphonates was recommended in a joint statement by several associations including  American Association of Clinical Endocrinologists (AACE) and National Osteoporosis Foundation (NOF). 

Duration of Treatment: Expert opinion 

Oral bisphosphonates treatment duration could be extended from 5 to 10 years and zoledronic acid treatment could be extended from 3 to 5 years if the patient has had prior vertebral fracture or if  their T-score stays less than or equal to -2.5 (Black, 2012).  Humerus fracture risk was not analyzed in the post-hoc data.  Remind patients that these drugs are not perfect and fractures can still occur while on treatment.  If this occurs, consider reviewing for secondary causes. 

The Dental Clearance

In the setting of treating a cancer patient, the general preference is to wait to start any bisphosphonates until after all dental procedures are completed. 

The risk of osteonecrosis of the jaw is very low (Khan, 2017; ACCE 2020 Guidelines see Figure 2). The best approach is to prevent it with regular dental check-up.  Routine dental work and cleanings can be done as usual without interrupting osteoporosis treatment.  If major invasive dental surgery or if the patient has major risk factors for osteonecrosis of the jaw, Dr. Crandall suggests holding anti-resorptive treatment until after the mucosa has healed which could be one to two months.  These major risk factors include: diabetes, glucocorticoid use, dentures, smoking, periodontal disease, and antiangiogenic agents.

CKD and Osteoporosis Treatment

Bisphosphonates are not recommended in patients with EGFR less than 30 due to lack of clinical experience.  Treatment options are limited.  Dr. Crandall noted that patients with CKD are at higher risk of having mineral disturbances, such as hypocalcemia, while on denosumab (Jalleh, 2018).  Using denosumab places the patient and provider in a conundrum since treatment duration is unknown and bisphosphonates, which are not indicated in patients with CKD, are recommended if/when denosumab is discontinued. 

Osteoporosis prevention starts with lifestyle

Dr. Crandall recommends weight-bearing and resistance exercises such as those used by National Osteoporosis Foundation as well as advising patients to limit alcohol use and avoid tobacco. Additionally, she advises providers to routinely assess fall risk.  Dr. Crandall reminds us that we don’t know the peak of the patient’s T-score so be more concerned about the rate of T-score decline than an initial low score.  

Vitamin D and Calcium 

Calcium and vitamin D sufficiency is important in the younger years to reach peak bone mass which occurs at 29 years of age.  The goal in the older patient population is to keep sufficient levels more from the diet than from supplements of calcium and vitamin D. Dr. Crandall suggests using the Institute of Medicine as an age- and sex-stratified metric for determining dietary intake.  

Regarding vitamin D, more is not necessarily better since excess vitamin D could be harmful. Aim to help patients replenish the 25-hydroxy vitamin D level to 20-30 ng/dl range and maintain that level (Dr. Crandall’s expert opinion).

Take home points 

One-quarter of the older women that should be screened for osteoporosis are being missed. Avoid overscreening the healthy women and focus on the underscreened women (White, 2017). 

Remember to recognize that spine, hip or wrist fractures are signs of osteoporosis disease. Don’t let the next fracture be a hip fracture! 

Links

1. Dr. Crandall’s Favorite Chips: Hawaiian Potato Chips

Goal

Listeners will confidently diagnose and monitor osteoporosis with bone mineral density testing,   discuss treatment options with patients and counsel patients on side effects. 

Learning objectives

After listening to this episode listeners will…  

1. Recall the basic definitions and diagnosis of osteoporosis and low bone density  
2. Select treatment based on patient’s lifestyle, comorbidities and risk factors
3. Navigate the discussion on side effects, including osteonecrosis of the jaw 
4. Engage patients in osteoporosis prevention and supplements 

Disclosures

Dr. Crandall reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures. 

Citation

Valdez I, Crandall C, Williams PN,, Watto MF. “#277 Bone Up on Osteoporosis in Primary Care”. The Curbsiders Internal Medicine Podcast. http://thecurbsiders.com/episode-list Air Date May 31, 2021.