Osteoporosis has long been framed as a disease of older women, but a new systematic review of randomized controlled trials is drawing attention to a population that clinicians have repeatedly overlooked: older men. The review, published in the journal Archives of Osteoporosis, synthesizes the available randomized evidence on both drug-based and non-drug strategies for managing osteoporosis in men, and its central message is sobering. While standard bone-building medications do reliably improve bone mineral density in men, the evidence that they actually prevent the fractures that matter most remains surprisingly thin, and the non-pharmacological alternatives—exercise and nutritional supplementation—rest on even shakier methodological ground.

The team, led by Marco Antonio Araújo da Rocha-Loures of the Clínica de Reumatismo in Maringá, Brazil, and supported by the Brazilian Society of Rheumatology, conducted an exhaustive search across eight major databases, including PubMed, EMBASE, Scopus, the Cochrane Library, Web of Science, SciELO, PEDro and LILACS, supplemented by gray literature sources. Their aim was to answer a deceptively simple question: in men with primary or secondary osteoporosis, which interventions actually reduce fracture risk and improve bone mineral density? The investigators followed the PRISMA reporting framework and used the Cochrane Handbook for systematic reviews, version 6.5, as their methodological backbone. Statistical analyses were performed in RStudio version 4.3.3, and the risk of bias in each included trial was assessed with the Cochrane RoB 2 tool, the current standard for evaluating randomized studies.

After screening the literature, the reviewers settled on twelve randomized controlled trials. Ten of these tested pharmacological interventions, one examined a nutritional supplement, and one evaluated an exercise program. The pooled study populations had a mean age of 60.9 years, with a standard deviation of 5.2 years, and baseline disease severity that qualifies as established osteoporosis by any conventional definition: average T-scores of minus 2.9 at the lumbar spine and minus 2.7 at the femoral neck. A T-score expresses how many standard deviations a person’s bone density lies below the young adult mean, and values below minus 2.5 define osteoporosis under World Health Organization criteria. These were not marginal cases; these were men with substantially compromised skeletons.

The pharmacological findings centered on two drug classes that dominate osteoporosis therapy worldwide. Bisphosphonates—represented in the included trials by alendronate and risedronate—work by binding to bone mineral and poisoning the osteoclasts, the cells that resorb bone, thereby tipping the delicate balance of bone remodeling toward formation. The antiresorptive effect is well documented, and the trials reviewed here confirmed that both agents produce measurable gains in bone mineral density at the spine and hip in men. Teriparatide, the second major therapy evaluated, takes the opposite mechanistic approach. As a recombinant fragment of human parathyroid hormone, comprising the first 34 amino acids, it is administered by daily injection and acts as an anabolic agent, stimulating osteoblasts to build new bone rather than simply slowing its loss. The landmark trial by Orwoll and colleagues, included in this review, demonstrated significant bone density gains in osteoporotic men treated with teriparatide, and a combination study testing risedronate alongside teriparatide explored whether pairing an anabolic with an antiresorptive agent yields additive benefits.

Yet when the reviewers looked beyond bone density to the outcome that ultimately matters—fractures—the picture became decidedly less reassuring. The effects of pharmacological treatment on fracture risk were described as inconsistent across the included trials. This is not because the drugs have been proven ineffective at preventing fractures; it is because the trials in men were generally too small, too short, or too sparsely powered to detect fracture reduction with statistical confidence. Fractures are relatively rare events even in osteoporotic populations over the time frames typical of clinical trials, and demonstrating a meaningful reduction requires thousands of patient-years of follow-up. Almost all of the definitive fracture data for bisphosphonates and teriparatide come from trials conducted predominantly in postmenopausal women, and regulators and guideline writers have long extrapolated those results to men. The new review makes clear how much of the male-specific evidence base rests on that extrapolation rather than on direct demonstration.

The non-pharmacological arm of the review offered some of its most intriguing, if preliminary, findings. A single exercise-based trial examined resistance training in men with secondary osteoporosis following hemiplegia, using weight-training sessions lasting 60 to 90 minutes per day. That regimen was associated with improvements in bone mineral density, consistent with the mechanistic understanding that mechanical loading stimulates osteogenesis through skeletal strain detected by osteocytes, which in turn signal osteoblast recruitment. The Wolff’s law principle—that bone adapts to the loads placed upon it—has underpinned exercise recommendations for skeletal health for over a century, but robust randomized evidence in older men with established osteoporosis has been scarce. The second non-pharmacological trial tested L-carnitine, a compound involved in mitochondrial fatty acid transport that has been hypothesized to influence bone metabolism through effects on osteoblast activity, and reported bone density benefits as well. Both findings, the reviewers caution, are limited by methodological constraints in the underlying studies, and neither can be considered practice-changing on its own.

Risk of bias across the twelve trials varied considerably, a finding that colors every conclusion the review can offer. The RoB 2 assessment examines domains including the randomization process, deviations from intended interventions, missing outcome data, measurement of outcomes, and selective reporting. Trials of older drugs conducted decades ago often fall short of contemporary standards for blinding, allocation concealment, and pre-registered outcome definitions. When the reviewers weighted the totality of evidence, they concluded that pharmacological therapies do improve bone mineral density in older men, but that the evidence remains insufficient to demonstrate consistent fracture risk reduction, and that non-pharmacological interventions show potential benefits supported only by limited evidence.

The clinical implications of these gaps are considerable. Osteoporosis in men is widely acknowledged to be underdiagnosed and undertreated, and the consequences of that neglect are severe: men account for a substantial fraction of hip fractures, and men who sustain a hip fracture experience higher mortality than women with comparable injuries. Vertebral fractures in men frequently go unrecognized, and secondary causes—including hypogonadism, glucocorticoid use, alcohol excess, and malabsorption—are common yet often uninvestigated. Guidelines from bodies such as the Endocrine Society have recommended bisphosphonates as first-line therapy for men at high fracture risk, but those recommendations rest in large part on bone density surrogates and on fracture data imported from female populations. Surrogate endpoints like bone mineral density correlate with fracture risk, but the correlation is imperfect, and treatments can produce density gains without proportional fracture reduction, as has been demonstrated in other therapeutic contexts.

What the review ultimately argues for is a new generation of adequately powered randomized trials in men, designed with fractures as the primary endpoint rather than bone density. Such trials are expensive and logistically demanding, requiring large sample sizes and multi-year follow-up, but the reviewers contend that they are the only way to place male osteoporosis management on the same evidentiary footing as postmenopausal osteoporosis. They also call for better-designed studies of non-pharmacological approaches, noting that exercise interventions in particular could offer fractal benefits—improved balance, muscle strength, and fall prevention—that drugs cannot provide, and that falls are the proximate cause of the majority of fragility fractures in older adults. An intervention that reduces falls while modestly increasing bone density could, in principle, deliver a combined fracture-prevention effect larger than either mechanism alone.

For the millions of older men living with low bone mass worldwide, the practical takeaways from the review are nonetheless reasonably clear. The existing pharmacological arsenal—bisphosphonates and teriparatide foremost among them—does increase bone density in men, and no signal of unexpected harm emerged from the analyzed trials, making continued use consistent with current guidelines a defensible clinical stance. At the same time, men and their physicians should not assume that the fracture-prevention benefits observed in women have been proven directly in men, and the review’s authors hope their work will spur both researchers and funders to close a gap that has persisted for decades. Bone health in aging men, long a footnote in osteoporosis research, is finally receiving the systematic scrutiny it has long deserved—and the scrutiny reveals just how much work remains to be done.

Subject of Research: Effectiveness of pharmacological and non-pharmacological interventions for osteoporosis in older men, evaluated through a systematic review of randomized controlled trials measuring bone mineral density and fracture risk

Subject of Research: Medicine

Article Title: Management of osteoporosis in older men: a systematic review of randomized trials of pharmacological and non-pharmacological strategies

Article References: da Rocha-Loures, M. A. A., de Freitas Zerbini, C. A., de Azevedo, E., Martinez, L. C., de Resende Guimaraes, M. F. B., Franco, A. S., Paupitz, J. A., Bezerra, M. C., Szejnfeld, V. L., Pereira Soares, M. R. M., Grizzo, F. M. F., da Silva, A. R. B., da Silva Reis, D. M., da Silva, D. S., & Waclawovsky, G. (2026). Management of osteoporosis in older men: a systematic review of randomized trials of pharmacological and non-pharmacological strategies. Archives of Osteoporosis, 21(1), Article 82. https://doi.org/10.1007/s11657-026-01709-6

Image Credits: AI Generated

DOI: 10.1007/s11657-026-01709-6

Keywords: osteoporosis, older men, bone mineral density, fracture risk, bisphosphonates, teriparatide, resistance exercise, L-carnitine, randomized controlled trials, systematic review, elderly, treatment

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Ophelia Keating. (September 6, 2026). Treating osteoporosis in older men: review of drug and lifestyle trials. Scienmag. https://scienmag.com/treating-osteoporosis-in-older-men-review-of-drug-and-lifestyle-trials/

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