Nancy E. Lane MD

Expert Perspectives
Nancy E. Lane, MD
Management of High-Risk Osteoporosis

Nancy E. Lane, MD

Dr Lane is an Endowed Professor of Medicine, Rheumatology, and Aging Research; director for the Center for Musculoskeletal Health; director of the K12 NIH Building Interdisciplinary Research Careers in Women’s Health (BIRCWH), and principal investigator of the NIH funded Program on Sex Differences in Musculoskeletal Diseases Across the Lifespan at the University of California at Davis School of Medicine.

For postmenopausal patients who present with severe osteoporosis in the absence of or with at least 1 fragility fracture, I would start them on an anabolic agent, such as teriparatide, abaloparatide, or the new antisclerostin antibody romosozumab. If a patient has severe osteoporosis without a fracture and has not been treated for it, and if anabolic agents cannot be used, I would treat with denosumab 60 mg every 6 months for a number of years.

Regarding monitoring response to therapy, over the past few years I have generally reduced the measurement of bone turnover markers. I do, however, use these measurements in 2 particular clinical situations. First, I check procollagen type 1 N-terminal propeptide (P1NP) levels when initiating an anabolic agent, repeating the measurement again after 6 weeks of therapy. If the P1NP level has not doubled, then the patient may either not be taking the medication or administering it inappropriately and needs more education. It is very important to check P1NP levels early in the treatment course because if the medication is being administered or stored inappropriately, it would be a waste of resources. The other situation in which I monitor bone turnover markers is when a patient is on a drug holiday from an antiresorptive agent. For these patients, I order either P1NP or carboxy-terminal crosslinked telopeptide of type 1 collagen (CTX-1) levels when treatment is paused and then every subsequent year that the patient is not on therapy. If these markers increase by ≥50%, I order bone mineral density (BMD) measurements to determine if patients have lost significant BMD and might require reinitiation of treatment. I do not order bone turnover markers when patients are being treated with denosumab because if denosumab is stopped, another antiresorptive agent needs to be initiated to prevent rapid bone loss and incident fractures.

With regard to the topic of optimal screening frequency using dual-energy x-ray absorptiometry, we have seen a significant change in the number of BMD tests that are being ordered, both to diagnose osteoporosis and for response to treatment. In general, I obtain BMD measurements for patients aged ≥65 years to determine if they have osteoporosis or have low bone density, and I perform a Fracture Risk Assessment Tool (FRAX) calculation to see if these patients meet the treatment threshold for 10-year risk for fracture. Typically, I repeat BMD measurements every 2 years. BMD testing that is performed at an interval of <2 years has the problem of being potentially inaccurate.

It is important to remember that patients being treated for osteoporosis can experience fractures while on therapy, as all medications that are currently approved for osteoporosis treatment reduce fracture risk, but this risk is not reduced to zero. Therefore, I do not necessarily change treatment immediately due to fracture occurrence, but I do assess BMD. If a patient has a fracture while on therapy and also has a decrease in BMD, then I may change the treatment. If a patient has a reduction in BMD greater than the least significant change while on an antiresorptive or anabolic agent, I would look for other causes of bone loss by repeating a secondary osteoporosis workup. If the findings are negative, I may consider switching therapy. However, if another medical problem is found during the secondary workup, I will address that problem and then recheck BMD after a certain period of time to see if the new treatment has stabilized the BMD. 

When addressing management strategies of postmenopausal women with osteoporosis and comorbid chronic kidney disease (CKD), my approach to osteoporosis in patients with stage 3 CKD or creatinine clearance of approximately 60 mL/min is not different than that for patients with normal kidney function.I use bisphosphonates, both oral and intravenous, until patients have a creatinine clearance or glomerular filtration rate (GFR) <35 mL/min. In some cases, I use bisphosphonates for patients with a GFR of 30 mL/min, but I will lengthen the bisphosphonate infusion time to approximately 30 to 45 minutes. If patients have renal insufficiency and need therapy to either prevent or treat osteoporosis, I frequently prescribe denosumab 60 mg every 6 months. Currently, there are no restrictions on the use of denosumab for patients with renal insufficiency; however, these patients can frequently have low serum calcium because of reduced synthesis of 1,25-dihydroxyvitamin D3 that helps to absorb the calcium from the gastrointestinal tract. Therefore, for at least 2 weeks before and after the denosumab injection, I recommend that these patients take both vitamin D3 and calcium citrate supplements. 

In risk-benefit discussions regarding the theoretical osteosarcoma risk associated with anabolic agents, I typically note that osteosarcoma was observed in rats treated with high doses of parathyroid hormone from age 6 weeks for 2 years. Because of these data, we do not treat patients who are at increased risk for osteosarcoma, including those for whom their growth plates have not fused and those who have had radiation to the skeleton as teenagers, as radiation increase the risk for osteosarcoma. The risk is almost 0 in most patients without these risk factors.

In summary, we have sufficient medications to treat and prevent osteoporosis, but we just do not know when we can safely put patients on drug holidays or how long they are protected while off the medications.  These issues represent the current knowledge gaps in managing osteoporosis.

Disclosure: Dr Lane declared affiliations with Amgen, Inc.