The role of osteoanabolic agents in the management of patients with osteoporosis

Figures & data

Table 1. Osteoanabolic agents (from US prescribing information).

	Teriparatide	Abaloparatide	Romosozumab
Dose	20 µg daily	80 µg daily	210 mg once monthly
Indication(s)	Treatment of postmenopausal women with osteoporosis at high risk for fracture or who have failed or are intolerant to other available osteoporosis therapy (1)	Treatment of postmenopausal women with osteoporosis at high risk for fracture	Treatment of postmenopausal women with osteoporosis at high risk for fracture
Route of administration	Subcutaneous injection by the patient with prefilled pen		Two subcutaneous injections of 105 mg by a healthcare professional
Treatment duration	Use for more than 2 years during a patient’s lifetime should only be considered if a patient remains at or has returned to having a high risk for fracture	Use of abaloparatide for more than 2 years during a patient’s lifetime is not recommended.	Limit duration of use to 12 monthly doses at a time but no lifetime limit
Refrigerate the drug	Yes	No	Not applicable
Contraindications	Hypersensitivity to teriparatide or its excipients	Hypersensitivity to abaloparatide	Hypocalcemia, sensitivity to romosozumab
Adverse reactions	Arthralgia, pain, nausea	Hypercalciuria, dizziness, nausea, headache, palpitations, fatigue, upper abdominal pain, vertigo	Arthralgia, headache
Warnings and Precautions	Avoid use in patients with increased risk of osteosarcoma [2] Risk of hypercalcemia, urolithiasis, orthostatic hypotension	Not recommended in patients at increased risk for osteosarcoma [2] Risk of hypercalcemia, urolithiasis, orthostatic hypotension	Serious cardiovascular events including cardiovascular death and non-fatal stroke and myocardial infarction Risk of hypocalcemia, osteonecrosis of the jaw; atypical femoral fracture

1. Also indicated for treatment of men with primary or hypogonadal osteoporosis at high risk for fracture and for treatment of men and women with osteoporosis associated with sustained systemic glucocorticoid therapy at high risk for fracture.

2. Includes patients with open epiphyses, metabolic bone diseases including Paget’s disease, bone metastases, or history of skeletal malignancies, prior external beam, or implant radiation therapy involving the skeleton, and hereditary disorders predisposing to osteosarcoma.

Figure 1. Vertebral and non-vertebral fracture incidence in treatment and placebo groups in separate pivotal trials with osteoanabolic agents in women with postmenopausal osteoporosis. Bar heights denote the incidence of fracture in the placebo and treatment groups. Relative risk reduction with 95% confidence interval is noted for each treatment group. The study names and duration (months) of follow-up are noted for each study. NOTE: Because of different patient populations and the different length of follow-up among the studies presented, comparison between studies is not appropriate. * Confidence interval not provided. PFT = Pivotal fracture trial [24]; ACTIVE = Abaloparatide comparator trial in vertebral endpoints trial [18]; FRAME = Fracture study in postmenopausal women with osteoporosis study [25]; RRR = relative risk reduction (95% confidence interval).

Table 2. BMD changes with osteoanabolic drugs compared to placebo.

Osteoanabolic drug	Study name and reference	Treatment interval	BMD Mean % difference from placebo
			Lumbar spine	Total hip	Femoral neck
Teriparatide	PFT [22]	~18 months	8.6%	3.6%	3.5%
Abaloparatide	ACTIVE [18]	18 months	10.4%	4.3%	4.0%
Romosozumab	FRAME [23]	12 months	13.3%	6.9%	5.9%

PFT = Pivotal Fracture Trial; ACTIVE – Abaloparatide Comparator Trial In Vertebral Endpoints;

FRAME = Fracture Study in Postmenopausal Women with Osteoporosis

Table 3. Fracture risk reduction with osteoanabolic agents vs anti-remodeling drugs.

Drug	Teriparatide			Teriparatide			Teriparatide			Romosozumab
Study (reference)	VERO [32]			Body [33]			Hadji [34]			ARCH [29]
Treatment interval (months)	24			14			18			12
	RIS	TPTD	RR (95% CI) P value	ALN	TPTD	RR (95% CI) P value	RIS	TPTD	RR (95% CI) P value	ALN	ROMO	RR (95% CI) P value
Vertebral fracture	12%	5.4%	56% (32, 71%) P = <0.0001	Not provided			9.4%	4.4%	53%* P = 0.01	6.3%	4.0%	37% (15–53%) P = 0.03
Non-vertebral fracture	6.1%	4.0%	34% (−10 to 61%) P = 0.10	13.7%	4.1%	70%* P = 0.042	8.3%	7.8%	6%* P = 0.89	4.6%	3.4%	26% (−1 to 46%) P = 0.057

* Confidence interval not provided.

VERO = Vertebral Fracture Treatment Comparisons in Osteoporotic Women; ARCH = Active-Controlled Fracture Study in Postmenopausal Women with Osteoporosis at High Risk; RIS = risedronate; TPTD = teriparatide; ALN = alendronate; ROMO = romosozumab; RR = risk reduction; CI = confidence limits.

Table 4. Direct comparisons of changes in BMD and estimates of bone strength with osteoanabolic agents.

Clinical studies (Reference)	Study participants	Duration of therapy	Measurement	Measurement site	Mean % change from baseline (SD or 95% CI)
Teriparatide vs abaloparatide					Teriparatide	Abaloparatide
Phase 2 study [45]	Treatment-naïve women with low bone density	24 weeks	BMD	Lumbar spine	5.5% (4.1%)	6.7% (4.2%)
				Total hip	0.5% (3.9%)	2.6% (3.5%)
ACTIVE trial [18]	Treatment-naïve women with postmenopausal osteoporosis	18 months	BMD	Lumbar spine	10.5%	11.2%
				Total hip	3.3%	4.2%
Teriparatide vs romosozumab					Teriparatide	Romosozumab
Phase 2 study [21, 46]	Treatment-naïve women with low bone density	12 months	BMD	Lumbar spine	7.1% (6.1, 8.2%)	11.3% (10.3, 12.4%)
				Total hip	1.3% (0.7, 2.0%)	4.1% (3.5, 4.8%)
			Estimated strength by FEA	Lumbar spine	18.5%	27.3%
				Total hip	−0.7%	3.5%
STRUCTURE study [47]	Bisphosphonate-treated women with low bone density	12 months	BMD	Lumbar spine	5.4% (4.7, 6.1)	9.8% (9.0, 10.5)
				Total hip	−0.5% (−1.0, −0.2%)	2.9% (2.2, 3.0%)
			Estimated strength by FEA	Lumbar spine	NA	NA
				Total hip	−0.7% (−1.5, −0.1)	2.5% (1.7, 3.2%)

SD = standard deviation; CI = confidence interval; BMD = bone mineral density; FEA = finite element analysis from computed tomography scans; NA = not available

Kendler DL, Bauer DC, Davison KS, et al. Vertebral fractures: clinical Importance and management. Am J Med. 2016;129(2):221 e1–10.

 Web of Science ®Google Scholar