Dr Sabashini Ramchand
The combination of high-dose teriparatide and denosumab is most likely to help prevent fractures in postmenopausal women, the ANZBMS 30th Annual Scientific Meeting has been told.
Presenting an update on combination therapy for postmenopausal osteoporosis, Dr Sabashini Ramchand said initial combination approaches combining two antiresorptive agents had not generally shown significant benefit over monotherapy.
“Most of these combinations were with hormone replacement therapy and bisphosphonates,” she said.
“More recently, a number of relatively small clinical trials have evaluated the effects of combining bone-forming agents, in particular PTH 1-34 and PTH 1-84, with a number of antiresorptive therapies.”
Dr Ramchand, from Melbourne but currently a research fellow in the endocrine unit at Massachusetts General Hospital and Harvard University, told the meeting that combination therapy with bisphosphonates and teriparatide produce different outcomes based on skeletal site.
“At the spine, increases in BMD [with combination therapy] are similar to teriparatide monotherapy. At the hip, increases in BMD are similar to bisphosphonate monotherapy in women who have not received prior bisphosphonate therapy.”
She noted that in patients receiving treatment with a bisphosphonate, overlapping treatment with teriparatide may have more beneficial BMD effects at both the spine and hip, compared to stopping the bisphosphonate and starting teriparatide.
“But only combination therapy with denosumab and teriparatide improves bone density, bone structure and estimated strength at both the hip and spine more than monotherapy with either drug alone,” she said.
“This treatment strategy may be useful in patients at high risk of fracture where rapid and large gains in bone density are required,” she said.
Research from her Harvard colleagues in the DATA-HD study, published last year in The Lancet Diabetes and Endocrinology, had found denosumab combined with high dose teriparatide (40 μg) had more beneficial skeletal effects than the denosumab combined with standard dose teriparatide (20μg).
More recently, Dr Ramchand led the DATA-HD HR-pQCT study which also confirmed that the combination improved peripheral bone density, trabecular microarchitecture, cortical microstructure, and estimated bone strength.
The 69 patients were randomised to receive either standard or high dose teriparatide (daily subcutaneous injection) for nine months, overlapped with denosumab (60 mg subcutaneous injection) at three, nine and 15 months.
The study, published in the Journal of Bone and Mineral Research, found that the benefits were again greater with high-dose versus standard dose teriparatide.
“Overall, combined denosumab with high-dose teriparatide appears to have some beneficial skeletal effects, particularly at the axial sites, compared to combination with standard-dose teriparatide.”
Clinicians will need to consider the issue of denosumab cessation, she said, and studies had shown a single dose of solendronate offered maintenance of BMD at 12 months and partial longer term protection.
She said long-term data on fracture incidence or surrogate end-points with combination therapy versus monotherapy was still required.
A cost-benefit analysis of combination therapy was also required.
Meanwhile a study using bone histomorphometry evaluation of iliac crest bone biopsies was underway to better understand the underlying cellular mechanisms at play with combination therapy.