Newswise — ATLANTA — New research presented at ACR Convergence, the American College Rheumatology’s annual meeting, reveals that romosozumab, an osteoporosis drug, produces substantial gains in bone mineral density in the hip and lumbar spine within one year, and that transitioning patients to a potent antiresorptive drug can lead to even more bone density gains (ABSTRACT #1973). 

Osteoporosis results from a loss of bone mass, measured as bone mineral density (BMD), and from a change in bone structure. Many factors will raise your risk of developing osteoporosis and breaking a bone. Bone is living tissue that is in a constant state of regeneration. The body removes old bone (called bone resorption) and replaces it with new bone (bone formation). 

Earlier studies have shown that another bone building medication, teriparatide, which stimulates both bone formation and bone breakdown, boosts BMD in both the spine and hip when used first, followed by an antiresorptive drug. However, when antiresorptive drugs are given first, particularly bisphosphonates, such as alendronate, and denosumab, the effect of teriparatide is different, and a patient’s BMD may decline in their hips. 

To find out more about how romosozumab may be given in sequence with different antiresorptive drugs, researchers launched this new study that reviewed results from four recent, large-scale trials.    

“Romosozumab exerts a unique mechanism of action on bone tissue. It increases bone formation and decreases bone resorption. When it’s given as initial therapy for one year, followed by an antiresorptive medication such as alendronate or densosumab, the treatment sequence significantly increases BMD and reduces fracture risk compared to both placebo and alendronate treatment,” says the study’s co-author, Felicia Cosman, MD, Professor of Medicine at Columbia University College of Physician and Surgeons in New York City. “This study was designed to determine if, despite the different mechanism of action for romosozumab versus teriparatide, the effect on BMD would be different when romosozumab was given as the second treatment, after an antiresorptive medication, compared to using romosozumab first.” 

The researchers found that osteoporosis patients had noticeably different results when romosozumab was administered first, rather than after, an antiresorptive treatment. In the two studies where romosozumab was given first, over the year of romosozumab treatment, patients’ total hip BMD increased 6% in one study and 6.2% in the other. In contrast, when they took alendronate first, the total hip BMD increased only 2.9% with romosozumab treatment. When denosumab was given first, the total hip BMD increased only 0.9% with romosozumab administration.  

Over two years, when romosozumab was followed by alendronate, the 2-year total hip BMD gain was 7.1% and when romosozumab was followed by denosumab, the 2-year total hip BMD gain was 8.5%.  In contrast, with the inverse sequence, when denosumab was given first, followed by romosozumab, the 2-year total hip BMD gain was less than half - only 3.8%. 

What about the effect of different treatment sequences on bone density in the lumbar spine? The researchers found similar results here. Over one year, when romosozumab was given first, patients’ spine BMD increased 13.7% in one study and 13.1% in the other. When romosozumab was given after alendronate, lumbar spine BMD gain was 9.8%. When romosozumab was given after denosumab, the spine BMD gain was only 5.3%.  

Similarly, over two years, when romosozumab was followed by alendronate, two-year spine BMD gain was 15.2%, and when romosozumab was followed by denosumab, two-year spine BMD gain was 16.6%. When denosumab was followed by romosozumab, two-year spine BMD gain was lower, at 11.5%.

Because women who have had recent or multiple fractures in adulthood are at very high risk for more, this data could help both osteoporosis patients and their doctors make more effective preventive treatment choices, says Dr. Cosman. 

“These women need medication that can build BMD fast to improve bone strength and reduce the risk of fractures. The standard approach that most health care providers use is to start treatment with antiresorptive medicine.  However, bone building agents like romosozumab, abaloparatide and teriparatide reduce fracture risk faster than antiresorptive medicines. There are about two million fractures every year from osteoporosis,” she says. “Patients need to know that the best option for them might be to receive a bone building medication first, rather than an antiresorptive treatment.”




About ACR Convergence

ACR Convergence, the ACR’s annual meeting, is where rheumatology meets to collaborate, celebrate, congregate, and learn. Join ACR for an all-encompassing experience designed for the entire rheumatology community. ACR Convergence is not just another meeting – it’s where inspiration and opportunity unite to create an unmatched educational experience. For more information about the meeting, visit, or join the conversation on Twitter by following the official hashtag (#ACR20).


About the American College of Rheumatology

The American College of Rheumatology (ACR) is an international medical society representing over 7,700 rheumatologists and rheumatology health professionals with a mission to empower rheumatology professionals to excel in their specialty. In doing so, the ACR offers education, research, advocacy and practice management support to help its members continue their innovative work and provide quality patient care. Rheumatologists are experts in the diagnosis, management and treatment of more than 100 different types of arthritis and rheumatic diseases.


ABSTRACT: Treatment Sequences with Romosozumab Before or After Antiresorptive Medication


Prior studies of anabolic/antiresorptive treatment sequences indicate that using teriparatide first followed by an antiresorptive results in greater bone mineral density (BMD) gains, particularly at the total hip, vs using an antiresorptive first followed by teriparatide (Cosman JBMR 2017). Romosozumab (Romo) increases bone formation while decreasing bone resorption, significantly increasing BMD and reducing fracture risk within 1 year. Here we summarize BMD data with Romo prior to or following an antiresorptive (alendronate [Aln] or denosumab [DMAb]).


We evaluated percentage change from baseline in BMD at the total hip and lumbar spine from four trials where patients received Romo prior to an antiresorptive (Phase 3 ARCH [Saag NEJM, 2017] and Phase 3 FRAME [Cosman, NEJM 2016]) or Romo following antiresorptive therapy (Phase 3 STRUCTURE [Langdahl, Lancet 2017] and Phase 2 [Kendler, OI 2019]). Percentage change from baseline BMD was assessed by either an ANCOVA (FRAME) or repeated measures (ARCH, STRUCTURE) model adjusting for baseline covariates, or as summary statistics (Phase 2).


Total hip BMD (Figure 1): In ARCH, BMD increased 6.2% with 1 year of Romo, and a total of 7.1% with the 2-year Romo/Aln sequence; and in FRAME, patients gained 6.8% with 1 year of Romo and a total of 8.8% with the 2-year Romo/DMAb sequence. Patients in STRUCTURE, who were previously treated for ≥1 year with Aln, gained 2.9% with 1 year of Romo. In a Phase 2 study, following 1 year of DMAb, 1 year of Romo increased BMD by 0.9%, for a total gain of 3.8% with the 2-year DMAb/Romo sequence.

 Lumbar Spine BMD (Figure 2): In ARCH, BMD increased 13.7% with 1 year of Romo, and a total of 15.2% with the 2-year Romo/Aln sequence; and in FRAME, patients gained 13.3% with 1 year of Romo and a total of 17.6% with the 2-year Romo/DMAb sequence. Patients in STRUCTURE (previously on Aln for ≥1 year) gained 9.8% with 1 year of Romo. In the Phase 2 study (after 1 year of DMAb), 1 year of Romo increased BMD by 5.3%, for a total gain of 11.5% with the 2-year DMAb/Romo sequence.


These data demonstrate that treatment with Romo first produces substantial BMD gains at the total hip and lumbar spine within 1 year, and that subsequent transition to a potent antiresorptive can augment those gains. In patients treated with Aln or DMAb, transition to Romo can improve BMD, though gains are not as large as those seen when Romo is used first. Since BMD on treatment is a strong surrogate for bone strength, our findings support the concept that high-risk patients should be offered treatment with Romo first, followed by transition to a potent antiresorptive.


Meeting Link: American College of Rheumatology Annual Meeting