One-year adolescent bone mineral density and bone formation marker changes through the use or lack of use of combined hormonal contraceptives

Rizzo, Anapaula da Conceição Bisi; Goldberg, Tamara Beres Lederer; Biason, Talita Poli; Kurokawa, Cilmery Suemi; Silva, Carla Cristiane da; Corrente, José Eduardo; Nunes, Helio Rubens Carvalho

doi:10.1016/j.jped.2018.05.011

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Original articles • J. Pediatr. (Rio J.) 95 (5) • Sep-Oct 2019 • https://doi.org/10.1016/j.jped.2018.05.011 copy

One-year adolescent bone mineral density and bone formation marker changes through the use or lack of use of combined hormonal contraceptives^☆ ☆ Please cite this article as: Rizzo AC, Goldberg TB, Biason TP, Kurokawa CS, Silva CC, Corrente JE, et al. One-year adolescent bone mineral density and bone formation marker changes through the use or lack of use of combined hormonal contraceptives. J Pediatr (Rio J). 2019;95:567-74.

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objective:

The objective of this study was to evaluate the effects of two low-dose combined oral contraceptives on bone metabolism in adolescents for one year.

Methods:

This was a quasi-experimental study. The adolescents were divided into three groups: oral contraceptives 1 (n = 42) (20 µg EE/150 µg desogestrel), oral contraceptives 2 (n = 66) (30 µg EE/3 mg drospirenone), and a control group (n = 70). Adolescents underwent anthropometric assessment and densitometry (dual-energy X-ray). Bone age and bone formation markers (osteocalcin and bone alkaline phosphatase) were evaluated. The oral contraceptives users were evaluated again after 12 months. Linear regression analysis was used to indirectly study the effect of each additional year of chronological age on anthropometric and densitometric variables as well as on bone markers in the control group.

Results:

At study entry, no significant differences were observed between the oral contraceptives 1, oral contraceptives 2, and controls in the analyzed variables. Linear regression analysis showed an increase in bone mineral density and bone mineral content for each additional year. There was a significant reduction in bone alkaline phosphatase levels; no significant difference was observed for osteocalcin in control individuals. Comparison of dual-energy X-ray variables at baseline and after one year showed no significant differences in the oral contraceptives 1 or oral contraceptives 2 groups. A significant reduction in bone alkaline phosphatase and osteocalcin levels was observed in both the oral contraceptives 1 and oral contraceptives 2 groups.

Conclusion:

Adolescent women gain peak bone mass during this phase of life. Two low-dose combined oral hormonal contraceptives were associated with lower bone gain and lower bone formation markers than in untreated controls.

KEYWORDS
Adolescents; Oral contraceptives; Bone density; Osteocalcin; Bone remodeling; Prospective study

	Control (n = 70)			OC1 (n = 36)			OC2 (n = 61)
	Med/Mean	Min	Max	Med/Mean	Min	Max	Med/Mean	Min	Max	p ^a a Mann-Whitney test for comparison between OC1 and OC2.	p ^b b Kruskal-Wallis test for comparison between the three groups.
Ages (years)	16.00	12.00	19.40	15.00	11.00	20.00	15.00	12.00	18.00	0.663	0.182
Bone age (years)	17.00	14.00	19.00	16.00	14.00	18.00	17.00	14.00	21.00	0.245	0.402
Weight (kg)	52.55	41.00	69.90	54.00	39.00	73.40	54.00	38.50	69.00	0.855	0.971
Height (m)	1.60	1.49	1.72	1.59	1.49	1.67	1.59	1.39	1.71	0.862	0.212
BMI (kg/m²)^c c ANOVA for comparison of means between the three groups.	20.30	16.44	26.78	21.35	17.1	26.78	21.50	15.82	26.86	0.512	0.052
Z-score for BMI^c c ANOVA for comparison of means between the three groups.	-0.02	-1.40	1.15	0.27	-1.39	1.27	0.24	-1.73	1.24	0.840	0.113
BMI (Percentile)^c c ANOVA for comparison of means between the three groups.	48.89	8.07	87.46	58.72	8.21	89.78	59.89	8.18	89.22	0.692	0.066
Lumbar BMD (g/cm²)	0.951	0.724	1.174	0.963	0.770	1.169	0.955	0.744	1.242	0.987	0.874
Lumbar BMC (g)	51.00	29.94	76.64	49.82	38.54	72.99	50.19	34.61	79.39	0.579	0.854
Z-score for Lumbar	-0.300	-1.800	1.630	0	-1.400	1.900	0	-1.800	2.400	0.774	0.637
Total body BMD (g/cm²)	1.017	0.859	1.205	0.995	0.845	1.130	1.017	0.884	1.240	0.152	0.213
Total body BMC (g)	1886.75	1260.69	2473.26	1848.59	1291.25	2130.32	1804.57	1377.30	2719.86	0.620	0.743
Z-score for Total body				-0.900	-1.900	1.800	-0.500	-1.900	1.800	0.219	0.219
Subtotal BMD (g/cm²)	0.886	0.753	1.043	0.874	0.726	0.950	0.888	0.790	1.161	0.077	0.185
Subtotal BMC (g)	1445.81	923.07	1901.61	1443.84	945.38	1609.56	1395.64	1032.23	2254.86	0.541	0.782
Fat Mass (g)	15,315.20	9539.10	29,019.90	16,111.70	7740.60	25,324.60	17,593.45	10,151.70	29,019.90	0.037	0.069
Lean Mass (g)	35,636.00	26,173.60	48,669.10	37,105.10	29,294.40	48,669.10	35,325.60	25,993.70	51,819.50	0.209	0.358
Total body fat %	29.400	20.400	41.800	29.100	20.000	38.500	32.550	19.600	41.300	0.002	0.008
BAP (U/L)	53.92	15.41	87.90	44.86	3.94	132.766	39.885	19.312	103.404	0.093	0.225
Osteocalcin (ng/mL)	6.68	1.12	30.11	8.00	1.711	25.998	10.427	0.269	28.146	0.295	0.301

Control
	β	p	95%CI
Bone ages (years)	1.04	<0.001	1.02	1.06
Weight (kg)	3.42	<0.001	3.30	3.54
Height (m)	0.10	<0.001	0.10	0.10
BMI (kg/m²)	1.33	<0.001	1.29	1.37
Z-score for BMI	0.01	0.342	-0.01	0.02
BMI (percentile)	3.31	<0.001	2.93	3.68
Lumbar BMD (g/cm²)	0.060	<0.001	0.058	0.06
Lumbar BMC (g)	3.223	<0.001	3.086	3.36
Z-score for lumbar	-0.012	0.105	-0.026	0.00
Total body BMD (g/cm²)	0.064	<0.001	0.062	0.07
Total body BMC (g)	117.21	<0.001	113.150	121.27
Subtotal BMD (g/cm²)	0.056	<0.001	0.055	0.06
Subtotal BMC (g)	89.36	<0.001	86.041	92.68
Fat mass (g)	1045.85	<0.001	974.54	1117.16
Lean mass (g)	2238.40	<0.001	2150.19	2326.62
Total body fat%	1.910	<0.001	1.82	2.00
BAP (U/L)	-5.19	<0.001	-7.24	-3.14
Osteocalcin (ng/mL)	-0.30	0.540	-1.23	0.65

	OC1								OC2
	Baseline (n = 36)			12 months (n = 36)					Baseline (n = 61)			12 months (n = 61)
	Med/Mean	Min	Max	Med/Mean	Min	Max	Z	p	Med/Mean	Min	Max	Med/Mean	Min	Max	Z	p
Ages (years)	15.00	11.00	20.00	16.00	12.00	19.00	-4.4	0.000	15.00	12.00	18.00	16.00	13.00	21.00	-5.6	0.000
Bone age (years)	16.00	14.00	18.00	18.00	15.00	18.00	-4.1	0.000	17.00	14.00	18.00	17.00	15.00	18.00	-4.9	0.000
Weight (kg)	54.00	39.00	73.40	54.10	39.80	90.00	-3.2	0.001	54.00	38.50	69.00	54.45	39.50	73.60	-2.9	0.004
Height (m)	1.59	1.49	1.67	1.58	1.49	1.68	-1.3	0.179	1.59	1.39	1.71	1.59	1.39	1.73	-3.4	0.001
BMI (kg/m²)^a a Paired t-test comparison between time points in OC1 and OC2.	21.35	17.10	26.78	23.11	17.00	31.89	-2.9	0.037	21.50	15.82	26.86	21.87	17.91	26.78	-2.5	0.450
Z-score BMI^a a Paired t-test comparison between time points in OC1 and OC2.	0.27	-1.39	1.27	0.52	-1.97	1.77	-1.2	0.175	0.24	-1.73	1.24	0.29	-1.58	1.26	-0.7	0.759
BMI (percentile)	58.72	8.21	89.78	66.71	2.42	96.20	-1.0	0.194	59.89	8.18	89.22	60.44	15.00	89.60	-0.9	0.908
Lumbar BMD (g/cm²)	0.968	0.771	1.169	0.983	0.798	1.091	-1.7	0.088	0.955	0.744	1.242	0.926	0.672	1.242	-1.6	0.116
Lumbar BMC (g)	49.82	38.54	72.99	50.88	34.07	65.49	-1.4	0.166	50.19	34.61	79.39	50.98	33.90	77.35	-0.8	0.437
Z-score for lumbar	0.000	-1.400	1.900	-0.200	-1.300	2.000	-1.7	0.081	0.000	-1.800	2.400	-0.250	-3.100	2.100	-2.8	0.005
Total body BMD (g/cm²)	1.000	0.845	1.130	1.000	0.864	1.144	-1.9	0.059	1.017	0.884	1.240	1.031	0.907	1.242	-1.6	0.102
Total body BMC (g)	1848.59	1291.25	2130.32	1829.99	1360.21	2153.10	-3.2	0.001	1804.57	1377.30	2719.86	1769.70	1512.99	2809.39	-0.3	0.751
Z-score for total body	-0.900	-1.900	1.800	-1.000	-2.200	0.800	-2.7	0.007	-0.500	-1.900	1.800	-0.700	-2.200	1.700	-2.3	0.021
Subtotal BMD (g/cm²)	0.874	0.726	0.950	0.874	0.730	0.938	-0.3	0.765	0.888	0.790	1.161	0.907	0.788	1.165	-1.9	0.055
Subtotal BMC (g)	1443.84	945.38	1609.56	1397.775	995.05	1602.94	-1.5	0.126	1395.64	1032.23	2254.86	1378.83	1107.32	2360.76	-1.2	0.224
Fat mass (g)	16,111.70	7740.60	25,324.60	17,270.35	8940.40	34,651.30	-3.3	0.001	17,593.45	10,151.70	29,019.90	18,817.90	11,719.50	28,551.00	-4.1	0.000
Lean mass (g)	37,105.10	29,294.40	48,669.10	36,420.85	28,945.30	53,000.10	-2.5	0.012	35,325.60	25,993.70	51,819.50	34,553.00	26,597.90	44,855.40	-0.2	0.873
Total body fat %	29.100	20.000	38.500	31.800	20.300	39.600	-3.2	0.001	32.550	19.600	41.300	33.800	23.400	41.600	-4.0	0.000
aBAP (U/L)	53.92	3.94	132.77	41.48	17.44	69.64	-2.1	0.080	43.10	19.31	103.40	27.14	11.70	51.70	-4.0	0.001
Osteocalcin (ng/mL)	8.00	1.71	26.00	4.69	1.93	17.92	-3.1	0.002	10.43	0.27	28.15	1.47	0.00	19.83	-4.1	0.000

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[1] * Corresponding author. E-mail:tamara@fmb.unesp.br (T.B. Goldberg).