Statins, Osteoporosis Dual Therapy—May Improve Bone Health for Some

Two studies advance osteoporosis understand—Statin users had better cortical bone properties, while bone density changes were favorable when dual therapy: teriparatide and abaloparatide

With Richard Eastell, MD, Mattias Lorentzon, MD, PhD, and E. Michael Lewiecki, MD

Treating osteoporosis optimally remains an ongoing challenge. Better [bone disease] management appears possible given the results from these two studies that expand on our understanding of bone remodeling, and which may help advance clinical practice decisions now, and going forward, as supported by these study findings.1,2

Statins may improve bone health in the lumbar spine.

In a study by a group of Swedish researchers, and published in the Journal of Clinical Endocrinology and Metabolism,1 they sought to tease out the association between cortical bone microstructure and statin use in older women. They found that the individuals who were taking a statin for hyperlipidemia demonstrated better cortical bone characteristics than those not on one of these cholesterol-lowering medications.

In a second study,2 these researchers compared the effects of teriparatide (Forteo) and abaloparatide (Tymlos) on lumbar spine bone density. Eastell et al found similar long-term increases in vertebral bone density as well as detecting early differences in the bone density between the two drugs; the findings were published in Osteoporosis International.2

Could It Be That Statins Provide an Unanticipated Boost to Bone Density?

As the Swedish researchers noted, the effects of statins on reducing cardiovascular risks are well known and, in recent years, evidence has been accumulating that they may also have a positive effect on bone health.

Some research has found the statins lead to an increase in bone formation and inhibit bone resorption via reducing osteoclastogenesis,3 according to Mattias Lorentzon, MD, PhD, professor, and head of geriatric medicine at the Institute of Medicine of Sahlgrenska Academy and  Sahlgrenska University Hospital in Molndal, Sweden.

They found a variety of interesting differences in the individuals taking a statin versus the group of non-users, including physical function,  prevalence of diabetes and body mass index—all important factors influencing bone mineral density (BMD).1

However, past study findings have been mixed, he said. Dr. Lorentzon noted that the conflicting findings might be explained to a lack of adjustment for relevant confounders. In this latest research, however, the investigators focused on whether statins were linked with volumetric BMD and bone microstructure, taking into account these common confounders.1

A Closer Look at Bone Density Changes in Statin Users vs. Non-Users

This population-based study followed 3,028 women (mean age 77.8 years) in the greater Gothenburg area in Sweden.1 These women provided responses to a questionnaire about their personal medical history, medications, and lifestyle practices. In all, 803 women in the cohort had been prescribed a statin to address a confirmed diagnosis of hyperlipidemia; they had a higher body weight, worse physical function, and were more likely to have cardiovascular disease and diabetes than those not taking a statin (P < 0.05).

Used high-resolution peripheral quantitative computed tomography, the researchers then measured the bone microstructure and geometry at the ultradistal and distal (14%) site of the radius and tibia of each participant.1

Those taking a statin had lower cortical porosity (radius, 2.2 vs. 2.5, tibia 5.2 vs. 5.4, P = 0.01.) They had higher cortical bone density (radius, 1008 vs. 1001, tibia, 919 vs. 914, P < 0.01) and greater cortical area (radius, 60.5 vs. 58.6, tibia, 150 vs. 146.7, P < 0.01.) The results were reported after confounders such as age, weight, smoking, other medications, and prevalent diseases were taken into account.1

Dr. Lorentzon concluded:  ''Use of statins is associated with better cortical bone characteristics in older women."

"This study [as far as we are aware] is the first to find that statin users have better microstructure in the cortical bone than statin nonusers," Dr. Lorentzon told EndocrineWeb. "This finding indicates that better cortical bone microstructure, which translates to stronger cortical bone, may be an important reason for the lower fracture risk associated with statin use in some studies,'' he said.

Statins May Prove Beneficial for Women Already Taking Them

E. Michael Lewiecki, MD, FACP, FACE, director of the New Mexico Clinical & Osteoporosis Center in Albuquerque, director of bone health TeleECHO at the University of New Mexico Health Sciences Center and vice-president of the Board of Trustees for the National Osteoporosis Foundation; reviewed the study for EndocrineWeb, as he was not involved in this trial. 

Dr. Lewiecki offered these takeaways from the study findings:

"Since statins and nitrogen-containing bisphosphonates both have inhibitory effects on the mevalonate pathway, it has long been suggested that statins might provide skeletal benefits, especially if a way could be found to deliver more of it to the bone," he said. "Some studies and meta-analyses of studies, mostly observational in nature, have shown an association between statin treatment and higher bone density."

These researchers ''used pQCT (high-resolution peripheral quantitative computed tomography) to examine bone geometry and microarchitecture at peripheral skeletal sites" to find that the statin users had better cortical bone properties than non-users,” said Dr. Lewiecki. “This is an interesting observation, although numerous potential confounders limit interpretation of the data, so the clinical relevance is uncertain. Large prospective randomized clinical trials are needed to evaluate the skeletal effects of statins before any clinical recommendations can be made on the use of statins in patients with bone disease' [such as osteoporosis].”

Comparing Bone Drugs to Measure Net Changes in Bone Density

A research team from University of Sheffield and the University of California evaluated the relationship between early PINP changes and subsequent changes in the BMD of the cervical spine following a protocol of abaloparatide and teriparatide therapy.2 This design incorporated the recommendation to use procollagen type I N propeptide (s-PINP) and serum carboxy-terminal cross-linking telopeptide of type I collagen (s-CTX) for bone resorption as references markers of bone formation from the International Osteoporosis Foundation.4

The researchers also adopted the use of an uncoupling index (UI)—the balance between bone formation and bone resorption—as they believed it would provide similar evidence of treatment response in these groups, and provide further support for bone remodeling changes.2

The investigators took blood samples from 189 women taking abaloparatide and 227 on teriparatide,   to measure bone turnover markers: s-PINP and s-CTA at baseline and one-, three-, 12- and 18 months. In addition, the BMD for all subjects was assessed using dual-energy X-ray absorptiometry (DEXA) every six months beginning at baseline and for the 1-1/2 year duration of the study. Correlations were calculated between the log ratio of BMD from baseline to three months, and the percent change in BMD from baseline to 18 months; in addition, an UI was calculated for each group.2

Lead author, Richard Eastell, MD, FRCP, FRCPath, FMedSci, professor of bone metabolism and director of the Mellanby Centre for Bone Research at Northern General Hospital in South Yorkshire, England shared his assessment of the study findings this way for Endocrine Web:

"The marker of bone formation (PINP) increased more in response to teriparatide than in response to abaloparatide and yet they both had similar effects on BMD. If anything, abaloparatide had a greater effect on hip BMD."

"This was a puzzle that we solved by taking into account the change in bone resorption markers. These increased with both treatments, but to a lesser extent with abaloparatide than teriparatide. Thus we solved the paradox by using an index of remodeling imbalance that showed that the net bone formation increased the same amount with both treatments and that is why the increases in BMD were similar."

Bottom line?  "PINP may be used to detect response to abaloparatide as they found that the greater the increase in PINP at three months, the greater the increase in spine BMD anticipated at 18 months," Dr. Eastell told EndocrineWeb. "However, for any given increase in PINP, the increase in spine BMD is greater for abaloparatide than for teriparatide."

His suggestion to clinicians: "Taking a blood test [in your patients] after three months' of treatment with abaloparatide is useful to make sure there is a good response to the therapy."

Net Change in Bone Resorption and Remodeling Offers Better Insight to Therapeutic Gains

"This study helps to explain why treatment with teriparatide and abaloparatide is followed by a similar increase in lumbar spine bone density despite teriparatide producing a greater increase in PINP, a biologic marker of bone formation," said Dr. Lewiecki, who was not involved in the study and reviewed the findings for EndocrineWeb.

"A significant finding was that the difference between PINP and CTX, expressed as the ‘uncoupling index (UI)’ was about the same for both drugs," he said. "It seems that the balance between bone formation and bone resorption is more important than the absolute increase in bone formation, or determining the bone density benefits at the lumbar spine," Dr. Lewiecki said. "At the same time, these results support the use of PINP in clinical practice for early assessment of long-term effects of both drugs.

Relevant disclosures: Radius Health, Inc., the maker of abaloparatide, funded the study led by Dr. Eastell. In addition, Dr. Eastell reported receiving grants and fees from Amgen, Alexion, Immunodiagnostic Systems and Roche, Lilly, D3 Biomedical Science Institutes and travel support from Radius Health. Lorentzon has received consulting fees from Radius Health, Amgen, UCB Pharma, Renapharma and Consilient Healthy, and received lecture fees from Amgen, Lilly, Meda, Renapharma and UCB Pharma. Dr. Lewiecki has consulted for or been a clinical investigator for Radius.  

Continue Reading:
Glucocorticoid-Induced Osteoporosis Management: New Guidelines
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