Knowledge Gap Exists on Combined Treatment Efficacy Assessed by Bone Biomarkers in Osteoporosis and Osteopenia

elderly man walking, physical activity, exercise
Study authors conducted a systematic review to assess the impact of physical activity interventions in combination with pharmacologic treatments on bone turnover biomarkers in patients with osteopenia and osteoporosis.

Limited data are available on the effect of physical activity interventions combined with pharmacologic treatment on bone turnover markers in patients with osteopenia and osteoporosis, according to findings from a systematic review published in Journal of Clinical Medicine.

Bone loss is asymptomatic and progressive; however, decreased bone mineral density is associated with an increased risk for fracture. There are various methods aimed at reducing fracture risk, including physical activity and drug therapy.

The aim of the current systematic review was to determine the effect of physical activity interventions combined with pharmacologic treatment on bone biomarkers in patients with osteopenia and osteoporosis.

Study authors performed a systematic literature search of MEDLINE (PubMed), Embase (Ovid), Cochrane Central Register of Controlled Trials (Central), and CINAHL (EBSCO) up to 2021 that included patients aged 45 years and older with osteopenia or osteoporosis and a combination of physical activity with pharmacologic treatment vs standard pharmacologic intervention and no exercise intervention. Studies without data on bone biomarkers and physical activity and those published before January 2011 were excluded from the analysis.

Of 511 records screened, 50 fulltext articles were assessed for eligibility and 49 were excluded for not meeting the inclusion criteria. Overall, only 1 study matched the eligibility criteria.

The randomized controlled study by Jepsen and colleagues included 35 postmenopausal women aged between 35 and 81 years in which researchers assessed the impact of combined whole-body vibration training and teriparatide treatment compared with teriparatide alone on bone turnover biomarkers.  

During the study follow-up, there was a significant improvement in both carboxy-terminal crosslinked telopeptide of type 1 collagen and procollagen type 1 N-terminal propeptide, which respectively reflected the antiresorptive and anabolic metabolic effects; however, no additional effects of the combined treatment were reported.  

Secondary outcome results showed statistically significant improvements in lumbar spine and bone mineral density at 6 and 12 months in the intervention group (6.47% and 8.90%, respectively) and the control group (3.48% and 6.65%, respectively), but there was no statistically significant improvement in total hip bone mineral density and bone microarchitecture. These data supported the use of bone biomarkers to monitor the effects of various modalities to treat osteopenia and osteoporosis.

“Overall, given the novel and unexplored features of this topic, as showed by the present systematic review, further investigations in this field are crucial to reduce the burden of socioeconomic costs and to improve the health status and quality of life in people with osteopenia and [osteoporosis],” the study authors wrote.


Marini S, Barone G, Masini A, et al. Current lack of evidence for an effect of physical activity intervention combined with pharmacological treatment on bone turnover biomarkers in people with osteopenia and osteoporosis: a systematic review. J Clin Med. 2021;10(15):3442. doi:10.3390/jcm10153442