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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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
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).
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)
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.
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.
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.
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.
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.
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.
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 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.
The ACP has not recommended teriparatide and abaloparatide as first-line 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).
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.
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.
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.
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.
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).
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!
Listeners will confidently diagnose and monitor osteoporosis with bone mineral density testing, discuss treatment options with patients and counsel patients on side effects.
After listening to this episode listeners will…
Dr. Crandall reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures.
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.
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